Breast Cancer In the Views of Foods, Herbs & Vitamins

By Kyle J. Norton

The prevalence of breast cancer has been acknowledged in the scientific community worldwide. Breast cancer widespread in women in Southeast Asian as a result of over 2 decades of economic prosperity caused by unhealthy diet is a major concern. The findings for effective treatments are ongoing with some successes, but to discover an effective prevention and treatment with little or no side effects has proven difficulty. According to statistic, the risk of getting invasive breast cancer during life time of a women is !".. #etections of tumorigenesis through self observation are still the best approach to cure breast cancer in early stage but reduction of the mortality has not been accounted even with e$tensively modern technology in the field of diagnosis and insurance protection in %estern world, needless to say of counties which have little. &merged suggestions of healthy diet with plenty vegetables and fruits' ('2(')( with change of life style'*('+(',( may be the only choice for women in reducing risk of the diseases. -. -n .oods /oints of 0iew -n fact, certain vegetables'1('"( and fruits'2(' 3( or chemical compounds in them have been found to effect the breast cancer lines, induced apoptosis of breast cancer cells by blocking the energy sources of the pathways, influencing the signal pathways of the proliferation of the cells or suppressing the promoted cancers genes. A. Cr cifero s !e"etables 4ruciferous vegetables are the group of vegetables belonging to the family Brassicaceae, including cauliflower, cabbage, cress, bok choy, broccoli etc. -sothiocyanate '-T4(, one of the major chemical constistuent found in 4ruciferous vegetables has been studied e$tensively over the past three decades with preclinical evidence for the efficacy of various -T4s against cancer in preclinical models. Ben5yl isothiocyanate, the derivative of isothiocyanate showed an effectiveness in influencing carcinogen metabolism and signaling pathways relevant to tumor progression and invasion' ( against 6#A76B72) 'breast cancer dell line(, human breast cancer $enografts'mutation tissues(' 2(, suppressing 87linked inhibitor of apoptosis '8-A/( protein e$pression of cancer cell line 64.71 by knockdown of the p+)'antigens( protein level# )(. -n 9er72 positive 'a most aggressive case of breast cancer(, indole7)7 carbinol, a naturally occurring compound found in cruciferous vegetables, used combination with paclita$el 'a mitotic inhibitor( synergistically

inhibited growth of 9er2!neu human breast cancer cells by arresting cancer cells in the :2'pre7mitotic $hase( and 6'nuclear division( phase and inducting apoptosis!necrosis' *(. -)4 used alone also inhibited 9er72breast cancer cell growth in a dose dependent manner as the compound up7 regulated Ba$'an apoptosis promoter(, down7regulated Bcl72'an apoptosis inhibitor( and, thereby, increased the ratio of Ba$ to Bcl72 favoring apoptosis' +(. %. &omatos Tomato is a red, edible fruit, genus Solanum, belonging to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose and often in green house. ;ycopene, a major carotenoid component of tomato has been known in research community with the property to attenuate the risk of breast cancer. -n a time and doses depended, the compound showed an anti7proliferative activity against &<'estrogen receptor(!/<'progesterone receptor( positive 64.71, 9&<27positive S=7B<7) and triple7negative 6#A76B7*," cell lines by arresting cell cycle at the :3 !: phase'interphase together 7 chromosomes replicate in preparation for cell division( at physiologically achievable concentrations'range( found in human plasma' ,( and -nhibition of the &<7positive 64.71 through the cell cycle progression, &<7negative 6#A76B72) cells through : phase cell cycle7arrest as well as apoptosis' 1(. There is a report of a lack of :ST/ e$pression in untreated 6#A76B7*,". ;ycopene treatment not only restored the :ST/ e$pression but also with 2 micro6, once per week for 2 weeks induced demethylation of <A<beta2 'tumor suppressor gene( and the 9->7 'a cell growth inhibitor(( genes in the noncancer 64. 3A fibrocystic breast cells' "(. '. Fi"s >7he$ane insoluble fraction '9-.( found in figs may be lesser known for its efficacy in breast cancer cell suppressive activity. The combination of 9-. and do$orubicin showed a greater inhibition on cell growth in '9uman ductal breast epithelial tumor cell line( T*1# cells and increased the incidence of cells undergoing apoptosis, when compared to e$hibited do$orubicin alone' 2(. The soluble fraction '&thyl acetate soluble fraction '&AS.(( in fig leave was also found to enhance the cytoto$ic effect of do$orubicin by changing the inhibition of cell cycle :'2(!6 to :' ( phase'23( and Acetone e$tract of .icus religosa leaf '.A&( e$erted its efficacy in irreversible inhibition of breast cancer cell growth with

moderate to$icity by stimulating the loss of mitochondrial membrane potential in multiple breast cancer cell lines and accelerated cell death through the photosensiti5ing effect'2 (. (. )arlic :arlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties. #iallyl trisulfide'#AS(, a derived organosulfur compounds '?S4s( suppressed the a ratio of viable cells in the culture of '9uman breast cancer cell line( 64.71 and 64.7 2a 'a non7tumorigenic epithelial cell line( cells respectively by decreasing the percent of cells in phase :'2(!6 and inducing apoptotic cell death as a result of up regulating Ba$ protein and p+)'cellular tumor antigen( protein e$pression'22(. #AS also enhanced the effect of eicosapentaenoic acid, a breast cancer suppressor, and decreased the effect of linoleic acid, a breast cancer enhancer and reduced the side effects caused by anti7cancer agents'2)(. -n the study of a protein fraction from garlic, the fraction was found to be more effective than the augment 4#"'@( T7cell infiltration into the tumor site, in inhibiting tumor growth more efficiently than garlic e$tract in enhancing the 4#"'@( T7cell infiltration into the tumor site'2*(. *. +$inach Spinach is an edible flowering plant in the genus Spinacia, belonging to the family of Amaranthaceae and native to central and southwestern Asia. -t is considered as a healthy plant containing vary vitamins and minerals. 4onsuming spinach may be a significantly protective effect on breast cancer among premenopausal women'2+(. &ating carrots or spinach more than twice weekly, compared with no intake, was associated with an odds ratio of 3.+, '2+A confidence interval 3.)*73.2 (, but does not distinguish among several potential e$planations for the protective association observed between intake of carrots and spinach and risk of breast cancer.'2,(. -t is said that included supplementation of A. gangeticus aBueous e$tract of red spinach in +A, 1.+A and 3A in cancer induced rats showed a induction of all tumor marker en5ymes especially at 3A.'21(. ,. Kel$ =elps are large seaweeds 'algae( growth under shallow in underwater of shallow oceans belonging to the class /haeophyceae in the order ;aminariales, with the thallus is used for food in many cultures. ;aminaria, a brown kelp seaweed containing a antibiotic substance, 7) beta

glucan, was effective in stimulating the host7mediated immune response and suggested of playing a essential role in preventing the initiation of breast cancer'2"(. Capanese seaweed ';aminaria angustata( e$tracts was also found to e$ert its antimutagenic effects in certain breast and colon carcinogen'22(. ;7tryptophana substances isolated from the kelp rhi5oid, may play an important role in in the inhibition of cell proliferation as an suggestion of increased tryptophan degradation occurred in women with early7stage breast cancer')3(') (. -. Chili $e$$ers 4hili pepper is the fruit of plants from the genus 4apsicum, belonging to the nightshade family, Solanaceae. The fruit has been used in human history for spices and cultivated for commercial profits. 4apsaicin 'trans7"7methyl7>7vanillyl7,7nonenamide(, a chemical constituent of chili peppers used in many cultures as anti cancer agent was found to inhibit the growth of &<7positive '64.71, T*1#, BT7*1*( and &<7negative 'S=B<7), 6#A76B2) ( breast cancer cell lines, reducing +3A the si5e of 6#A76B2) breast cancer tumors')2(, inducing cellular apoptosis through a caspase7independent pathway in 64.71 cells'))(. -n the comparison of capsaicin and #ohevanil, synthesi5ed from #9A and vanillylamine 'precursor to capsaicin(, researchers showed that the e$hibited effects of both vanilloids and dohevanil in growth inhibition and #>A fragmentation induction in 64.71 cells, but dohevanil was more potent than capsaicin')*(. .. Carrot 4arrot can grow to )ft tall. -t is root vegetable with orange color normally, a sub spices of #aucus carota, belongs to the family Apiaceae, native to Asian and &urope. -ntake of cruciferous vegetable and carrot are inversely associations with risk of estrogen receptor7negative!progesterone receptor7negative breast cancer')+(. %ild carrot or #aucus carota ;. ssp. carota 'Apiacea( oil e$tract, used in traditional medicine in ;ebanon and in different regions throughout the world was found to inhibit human colon '9T722, 4aco72( and breast '64.71, 6#A76B72) ( cancer cell lines, causing significant increase in cell death and decrease in cell proliferation'),(. B. &y$es of fr it may red ced ris/ of breast cancer 0. Bl eberry Blueberry is a flower plant, belonging to the family &riaceae and native to >orthern America. -t can grows from 3 cm to * metres tall.

Triple7negative breast cancer T>B4, a cancer does not e$press the genes for estrogen receptor '&<(, progesterone receptor'/<(, and 9&<2'gene( affecting appro$imately +A of all caner cases. .emale 6#A76B72) tumor7bearing mice fed with high fat diet with +A whole blueberry powder 'BB(, showed an inhibited T>B4 and T>B47related metastasis by reducing inflammation via specific cytokine7driven pathways with generation of an immune response to reduce tumor growth and metastasis'*3(. -n 1D7 estradiol7mediated mammary tumorigenesis, +A blueberry diet, showed to reduce tumor volume and multiplicity significantly, by down regulation of 4E/ A 'en5ymes, able to activate compounds with carcinogenic properties( and &<7F 'a receptor activated by the se$ hormone estrogen(genes e$pression and also favorable modulation of micro<>A 'mir7 "a and mir7)*c( levels in gene regulation'* (. ?ther chemical constituents anthocyanin and an anthocyanin7pyruvic acid adduct e$tract of blueberry were found to inhibited cancer cell proliferation by acting as cell antiinvasive factors and chemoinhibitors'*2(. %. A!ocado Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green7skinned, pear7shaped fruit that ripens after harvesting and native to the 4aribbean, 6e$ico, South America and 4entral America, belonging to the flowering plant family ;auraceous. -t is suggested that avocado7produced to$in persin may contain a positive anti breast cancer effect'*)(, /ersin selectively induces a :276 cell cycle arrest and cell death through caspase7dependent pathway'**(. ?thers in the study of the same, persin showed a anti breast cancer effect in both estrogen receptor '&<( and &<7negative breast cancer cells'*+(. '. +trawberry Strawberries is a genius of .ragaria G ananassa belonging to the family <oseaceae. They have been grown all over the world with suitable climate for commercial profits and for health benefits. 6ethanolic e$tract of strawberry '6&SB( fruits showed to induced cytoto$icity in cancer cells, irrespective of origin, in a concentration7 and time7dependent manner, in the testing against leukaemia '4&6( and breast cancer 'T*1#( cell lines through -nduction of intrinsic pathway of apoptosis by activating p1) 'a tumor suppressor( in breast cancer cells, when tumor suppressor gene p+) was mutated'*,(. /olyphenols, a major chemical component found in strawberry, as an e$tract, induced cytoto$ic with doses of appro$imately +3 microg!ml, causing a +3A

reduction in cell survival in both the normal and the tumour lines, including '64.71( breast cancer cell lines'*1(. -n other study, free5e7dried fruits of two strawberry cultivars ethanol e$tract, strongly inhibited 4aSki and Si9a cervical cancer cell lines and 64.71 and T*17# breast cancer cell lines'*"(. (. 1ome"ranate 1ome"ranate is a fruit7bearing small tree, genus /unica, belonging to family ;ythraceae, native to -ran but has been cultivated in Asian since ancient time. /omegranate e$tracts and genistein were found to e$ert their anti cancer effect in growth inhibition of cell proliferation and induction of apoptosis in human breast cancer cells'64.71( in doses and time depending manner'*2( by downregulated 9< genes 'a ubiBuitous cellular pathway that mediates transfer of genetic information( and increased e$pression of micro<>As 'mi<>As(, mi<7 ") 'predicted target <A#+3( and mi<72* 'regulation of gene e$pression('+3(. /omegranate fruit e$tracts '/.&s(, in dose7dependent inhibited >.7kB7dependent reporter gene responses associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing <ho4 and <hoA protein e$pression as these genes are associated with tumor cell invasion and metastasis'+ (. ,. )ra$es <esveratrol, a polyphenolic compound known as a good chemopreventive agent for inhibiting carcinogenesis processes that target the regulators of cell function and #>A replication, found abundantly in grapes, berries and peanuts are associated to reduced risk of breast caner. 9S7 12), a synthetic version of the compound induced :2!6'#>A damage checkpoint( arrest in the cell cycle progression in both types of cells and involved in cell7cycle arrest and probably in induction of p+)'tumor suppressor gene(7dependent apoptosis in 64.71 cells'+2(. 4atechin '<H4(, a polyphenol, was found to be effective in inhibiting mammary tumor growth and metastasis, by reduced Akt'multiple cellular processes activity, induced the activation of A6/='cellular energy(, and inhibited mT?<'mediate cellular responses( signaling in breast cancer cells'+)(. -n 9er72 breast cancer, fo$ grape seed e$tract increased the e$pression of Ba$'an apoptosis promoter( and A-.'Apoptosis inducing factor(, and decreased total /A</'cellular processes( e$pression, leading to significant downregulation of 9er72 in 64.71 cells'+*(. -. 1inea$$le

/ineapple is a species of Ananas 4omos, belonging to the family Bromeliaceae and native to southern Bra5il and /araguay. Today it is widely cultivated for commercial uses. -ts rich of vitamins and mineral and digesting en5yme bromelin seems to help digestion after a high protein meal. -t is a second only to banana as AmericaIs most favourite tropical fruit. Bromelain, a major chemical constituent or herb used in traditional medicine found in pineapple has e$erted its anti7metastasis of breast cancer by up regulating the function of c7Cun >7terminal kinase in cell proliferation, differentiation, survival and migration and p)" kinase to cause programmed cell death'+,(. -n :-7 3 A breast cancer cells, bromelain induced cell death via activation of the apoptosis mechanism, in increased dose7 dependent by promoting apoptosis and cytokine processing of caspase72 and caspase7) coinciding with elevation of serum 4= " levels'+,(. -n the br6#A76B72) mammary carcinoma, oral administration of bromelain increased the reduced b6A=7 and 6A=7cell activity in cell cycle regulation from 1."A to +*A 'b6A=7cell activity( and from ,A to *1A '6A=7cell activity by stimulating the deficient monocytic cellular cytoto$icity of mammary tumor'+1(. .. A$$le A$$le is the pomaceous fruit of the apple tree, a species of the rose family <osaceae. -t is one of the most widely cultivated tree fruits originated in 4entral Asia. -n estrogen7dependent 64.71 and estrogen7independent 6#A76B72) breast cancer cell lines, apple phytochemical e$tracts significantly inhibited cell proliferation in a dose7dependent manner and cell cycle modulation'+"(. -n breast carcinoma 6cf71 and 6cf71J9er " cells, peels of apple was found to be effective in antiproliferation accompanied by a :37 : phase arrest in cell cycle of breast cancer cells by a tumor suppressor protein that suppressed the regulation of cell invasion, metastasis, and angiogenesis'+2(. Study of apple e$tracts and Buercetin )7beta7d7glucoside combination, also showed to possess the synergistic effect in 64.71 cell proliferation',3(. 2. 3ran"e ?range is a species of 4itrus Sinensis, belonging to the family <utaceae and native to the Southeast Asia. ?range is round citrus fruits with finely7 te$tured skins, orange in color and one of most popular fruits in the world. /olymetho$yflavones '/6.s(, a chemical compound found in Sweet orange '4itrus sinensis ;.( peel, showed to induce 4a'2@(7mediated apoptosis in

human breast cancer cells by induced proapoptotic activity', (. #7limonene, another compound in orange peel oil, in rodent studies, also e$hibited its chemotherapeutic activity against mammary cells, through the induction of tumor cell apoptosis, tumor redifferentiation, and!or suppression of key proteins of cell growth7regulating ',2(. C. 3thers 0. Blac/ 4ice Black <ice is a type of rice with enriched Anthocyanins. including -ndonesian black rice and Thai jasmine black rice. -t has been considered as one of nature super foods with vary antio$idants. Anthocyanins in black rice, with oral administration of A&B< ' 33 mg!kg!day( to BA;B!c nude mice bearing 6#A76B7*+) cell $enografts significantly suppressed tumor growth and angiogenesis by suppressing the e$pression of the physiological process factors 66/7266/72' en5ymes involved in the breakdown of e$tracellular matri$(, and u/A'activator( in tumor tissue. Altogether, this study suggests the anticancer effects of A&B< against human breast cancer cells by inducing apoptosis and suppressing angiogenesis')1(')"(. ?ther chemical constituents of species of black glumedK >javara '?ry5a sativa ;.( isolation, namely, flavonolignans, tricin *I7?7'erythro7D7guaiacylglyceryl( ether 'compound ( and tricin *I7?7'threo7 D7guaiacylglyceryl( ether 'compound 2(, were also found to e$ert its effect on breast cancer cell line 64.71, causing apoptosis at concentration *3 and )3 Lg! by decreasing protein in the mitochondrial membrane, leading to chromatin condensation')2(. %. )reen tea :reen tea contains more amount of antio$idants than any drinks or food with the same volume, and is the leaves of 4amellia sinensis, undergone minimal o$idation during processing, originated from 4hina. :reen tea has been a precious drink in traditional 4hinese culture and used e$ceptional in sociali5ation for more than *333 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world. As suggestions, regular green tea intake has been associated with an inverse risk of breast cancer, as green tea enhanced the production of =i7,1, a cancer antigen when compare to women who do not.',)(. '7(7 epigallocatechin gallate, a phytochemical in green tea was found to e$ert its epigenetic effects in altering the #>A methyltransferase e$pression in many types of cancer, including breast cancer',*(. 4atechins, another

phytochemical of green tea, inhibited proliferation of breast cancer cells and blocked carcinogenesis in breast cancer probably through the e$pression of translocation across membranes or for degradation, ribonucleoprotein #>A reduplication, apoptotic cascade, etc.',+(. -n inflammatory breast cancer, a most aggressive type of breast cancer, green tea polyphenol epigallocatechin7)7gallate '&:4:(, showed decreased e$pression of genes that promote proliferation, migration, invasion, and survival in human breast cancer cell lines, SM67 *2 and SM67 23 by reduced lymphangiogenesis7 promoting genes',,( and inhibited the cell proliferation at 12 hours, after 3 micro6 of &:4: treatment. These suggested a possible reactivation of apoptosis, may be through the comple$ity of the angiogenic switch leading to the modulation of the cell migration processes against triple negative breast cancer cells',1(. -n human breast cancer 64.71 cells, selenium containing polysaccharides 'Se7:T/s( from a new variety of selenium7 enriched Niyang green tea, in dose7dependent, e$hibited an effective cell growth inhibition by inducing 64.71 cancer cells to undergo :2!6'cell cycle( phase arrest and apoptosis by an up7regulation of p+) 'tumor antigen( e$pression',"(. Mnfortunately, epidemiological data, on incidence of breast cancer and recurrence of breast cancer, consumption of + or more cups of green tea a day showed a non7statistically significant trend towards the prevention of breast cancer development. &vidence indicates that green tea consumption may possibly help prevent breast cancer recurrence in early stage '- and --( cancers',2(. '. 4ed wine <ed wine, made from the pigments of grape varieties is a wine involved e$traction of color, and flavour components from the grape skin. <ed wine phenolics piceatannol and myricetin showed to inhibit the profileration of estrogens hormone7dependent breast cancer cells by binding to the gene e$pression of estrogen receptor '&<( alpha, which interacts with responsive #>A seBuences located within the promoter region of target genes'13(. 4atechin hydrate '49(, an antio$idant in red wine, induced apotoposis against 64.71 cells, with the rate of *3.1A and * . ,A in the volume of +3 Lg!ml 49 in 2* hours, respectively. 6oreover, a *"7hour e$posure to +3 Lg!ml 49 and )33 Lg!ml 49 resulted in *).1)A and +2.2+A apoptotic cells, through its ability to increase the e$pression of pro7 apoptotic genes such as caspase7), 7", and 72 and T/+)'1 (. (. Blac/ bean Blac/ bean is a Small roughly ovoid legumes with glossy black shells,

genus /haseolus, belonging to the family .abaceae and can bought in most grocery stores all around the year in dried and canned forms. -t is believed that black bean was first domesticated growth in South America. %ater7soluble condensed tannins isolated from black beans showed inhibition against breast cancer cell line 64.71 at 2* micro6 by suppressed fetal bovine serum 'blood fraction remaining after the natural coagulation of blood( stimulated cell migration and the secretion of matri$ metalloproteinase72 '66/72 or gelatinase A(, matri$ metalloproteinase72 '66/72 or gelatinase B('involved in the breakdown of e$tracellular matri$(, and vascular endothelial growth factor 0&:.' ,+('regulator of angiogenesis( receptors e$pression'12(. /hytochemical of black bean '/haseolus vulgaris( seed coats, also enhanced potent antio$idant and antiproliferative activities against 64.71 human breast cancer cells in doses depending manner'1)(. *. Fermented soybean .ermented soybean made from ground soybeans, is an popular ingredient used in cuisines of &ast and Southeast Asia. 4hungkookjang, a =orean fermented soybean, containing high concentration of isoflavones and peptides showed to inhibit the growth of breast cancer 64.1 cells in decreased dependent on the concentration by activating T:.D pathway in cellular processes and depressing inflammation'1*(. -n murine breast adenocarcinoma, fermented soy product '.S/( showed an effectiveness in tumor containment with smallest tumor volumes. &$pressed larger amounts of nitric o$ide and -;7 D 'regulation of immune and inflammatory responses( and e$hibited larger tumor si5es'1+(. ,. 1ean t /eanuts is belong to the the legume related to the bean family and first cultivated in the in the 4haco region of /araguay and Bolivia. ;ectin ' '/>A(, a chemical constituent of peanut was effective in inhibiting proliferation of human breast cell lines 'N<71+. and 1)*7B('1,( and 64.7 1, T *1#, 9B; 33, BT 23'11(. Beta7Sitosterol found in legumes, oil seeds and unrefined plant oils such as peanut butter, pistachios and sunflower, showed to e$hibit the e$trinsic apoptotic programmed cell death pathway in human breast 64.71 and 6#A76B72) '1"(. -. Fa5seed .la$ seed is native to the region of the eastern 6editerranean to -ndia and also known as common fla$ or linseed. .la$, an erect annual plant, can grow

to .2 m tall. The leaves are 23O*3 mm long and ) mm broad. Study of athymic mice fed with basal diet 'control(, or 3A .S diet, with or without T<AS '2.+mg!kg( treatment for + wk, showed a positive effects in reduced tumor si5e and increased tumor apoptosis. #ietary .S improved the function of T<AS in increased overall survival'12(. -n dietary fla$seed lignan or oil combined with tamo$ifen showed an enhancing effect in reducing growth of estrogen receptor positive breast tumors '64.71( at low circulating estrogen levels by inhibiting cell proliferation, e$pression of genes, and proteins involved in the &<7 and growth factor7mediated signaling pathways'"3(, with .? greatest effect in increasing apoptosis compared with TA6 treatment alone'"3(. ;ignans 'a class of phytoestrogens( consumption was associated with a significant reduction in breast cancer risk'" (. -n estrogen7receptor7positive '64.71( and estrogen7 receptor7negative '6#A76B72) ( cells, .la$seed sprouts induced apoptosis and inhibited cancer cell growth by significantly upregulated p+)'Anti tumor antigen( m<>A 'transmits genetic information from #>A to the cytoplasm and controls certain chemical processes in the cell( in both cell cancer lines'"2(. 6any hours have been spent, hundred studies have been read, they may be worthless, if this article can not induce some women to change their diet patterns toward plenty vegetables and fruits accompanied with healthy style of living. 0egetables and fruits in the article, indeed, showed a positive effect in inhibiting proliferation and causing apoptosis in many breast cancer cell lines. But with e$pansions of :6?s into almost all food sources in production of large scale, approved by .#A and promoted by elective officials for commercial profits with lack of long term studies, organic farming are sitting in the defendant corner waiting for the death sentence in the ne$t super gene of :6?s cross7contamination. %ill the foods in this article be the same in the futureP %ill they still e$ert their anti breast cancer effectsP..... Chinese +ecrets &o Fatty 6i!er And 3besity 4e!ersal Mse The <evolutionary .indings To Achieve ?ptimal 9ealth And ;oose %eight Back to 6ost common Types of 4ancer httpJ!!kylejnorton.blogspot.ca!p!blog7page.html

Back to =yle C. >orton 9ome page httpJ!!kylejnorton.blogspot.ca 4eferences ' ( -ntake of specific fruits and vegetables in relation to risk of estrogen receptor7negative breast cancer among postmenopausal women by .ung TT, 4hiuve S&, %illett %4, 9ankinson S&, 9u .B, 9olmes 6#.'/ub6ed( '2( .ruits, vegetables and breast cancer riskJ a systematic review and meta7 analysis of prospective studies by Aune #, 4han #S, 0ieira A<, <osenblatt #A, 0ieira <, :reenwood #4, >orat T.'/ub6ed( ')( /remenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients. .reudenheim C;, 6arshall C<, 0ena C&, ;aughlin <, Brasure C<, Swanson 6=, >emoto T, :raham S.'/ub6ed( '*( ;ife style and risk of development of breast and ovarian cancer by /iQta B, 4hmaj7%ier5chowska =, ?pala T.'/ub6ed( '+( &pidemiological evidence for a relationship between life events, coping style, and personality factors in the development of breast cancer by Butow />, 9iller C&, /rice 6A, Thackway S0, =ricker A, Tennant 44.'/ub6ed( ',( &pidemiological correlates of breast cancer in South -ndia by Babu :<, ;akshmi SB, Thiyagarajan CA.'/ub6ed( '1( #ietary organic isothiocyanates are cytoto$ic in human breast cancer 64.71 and mammary epithelial 64.7 2A cell lines by Tseng &, Scott7 <amsay &A, 6orris 6&.'/ub6ed( '"( Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by :ST genotype by '2( &$tracts of strawberry fruits induce intrinsic pathway of apoptosis in breast cancer cells and inhibits tumor progression in mice.by Somasagara <<, 9egde 6, 4hiruvella ==, 6usini A, 4houdhary B, <aghavan S4. '/ub6ed( ' 3( Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry e$tracts inhibit growth and stimulate apoptosis of human cancer cells in vitro.by Seeram >/, Adams ;S, Nhang E, ;ee <, Sand #, Scheuller 9S, 9eber #.'/ub6ed( ' ( Ben5yl isothiocyanateJ double trouble for breast cancer cells by <ao 40.'/ub6ed( ' 2( -nhibition of human breast cancer $enograft growth by cruciferous vegetable constituent ben5yl isothiocyanate by %arin <, 8iao #, Arlotti CA, Bommareddy A, Singh S0.'/ub6ed(

' )( p+)7-ndependent apoptosis by ben5yl isothiocyanate in human breast cancer cells is mediated by suppression of 8-A/ e$pression by =im S9, Singh S0.'/ub6ed( ' *( ),)I7diindolylmethane and paclita$el act synergistically to promote apoptosis in 9&<2!>eu human breast cancer cells by 6c:uire =/, >goubilly >, >eavyn 6, ;an5a7Cacoby S.'/ub6ed( ' +( Translocation of Ba$ to mitochondria induces apoptotic cell death in indole7)7carbinol '-)4( treated breast cancer cells by <ahman =6, Aranha ?, :la5yrin A, 4hinni S<, Sarkar .9.'/ub6ed( ' ,( Anti7proliferative and apoptosis7inducing activity of lycopene against three subtypes of human breast cancer cell lines by Takeshima 6, ?no 6, 9iguchi T, 4hen 4, 9ara T, >akano S.'/ub6ed( ' 1( R&ffect of lycopene on the proliferation of 64.71 and 6#A76B72) cellsS. RArticle in 4hineseS by %ang A9, Nhang ;S.'/ub6ed( ' "( 6odulation of gene methylation by genistein or lycopene in breast cancer cells, by =ing7Batoon A, ;es5c5ynska C6, =lein 4B.'/ub6ed( ' 2( 4ombinational effects of he$ane insoluble fraction of .icus septica Burm. .. and do$orubicin chemotherapy on T*1# breast cancer cells by >ugroho A&, 9ermawan A, /utri ##, >ovika A, 6eiyanto &, =awaichi 6. '/ub6ed( '23( Synergistic effects of ethyl acetate fraction of .icus septica Burm. f. and do$orubicin chemotherapy on T*1# human breast cancer cell line by >ugroho A&, 9ermawan A, /utri # /, 6eiyanto &, 9akim ;.'/ub6ed( '2 ( Ba$ translocation mediated mitochondrial apoptosis and caspase dependent photosensiti5ing effect of .icus religiosa on cancer cells by 9aneef C, /arvathy 6, Thankayyan < S=, Sithul 9, Sreeharshan S. '/ub6ed( '22( :arlic constituent diallyl trisulfide induced apoptosis in 64.1 human breast cancer cells by 6alki A, &l7Saadani 6, Sultan AS.'/ub6ed( '2)( Anticancer effects of garlic and garlic7derived compounds for breast cancer control. Tsubura A, ;ai E4, =uwata 6, Mehara >, Eoshi5awa =.'/ub6ed( '2*( /urif ied /rotein .raction of :arlic &$tract 6odulates 4ellular -mmune <esponse against Breast Transplanted Tumors in BA;B!c 6ice 6odel by &brahimi 6, 6ohammad 9assan N, 6ostafaie A, Nare 6ehrjardi >, :ha5anfari T.'/ub6ed( '2+( .ood sources of phytoestrogens and breast cancer risk in 6e$ican women by Torres7STnche5 ;, ;Upe574arrillo ;, ;Upe574ervantes 6, <ueda7 >eria 4, %olff 6S.'/ub6ed(

'2,( -ntake of carrots, spinach, and supplements containing vitamin A in relation to risk of breast cancer by;ongnecker 6/, >ewcomb /A, 6ittendorf <, :reenberg &<, %illett %4'/ub6ed( '21( /otential anticancer effect of red spinach 'Amaranthus gangeticus( e$tract by Sani 9A, <ahmat A, -smail 6, <osli <, &ndrini S.'/ub6ed( '2"( The dietary intake of ;aminaria, a brown seaweed, and breast cancer prevention by Teas C.'/ub6ed( '22( &ffect of Capanese seaweed ';aminaria angustata( e$tracts on the mutagenicity of 1, 27dimethylben5RaSanthracene, a breast carcinogen, and of ),2I7dimethyl7*7aminobiphenyl, a colon and breast carcinogen by <eddy BS, Sharma 4, 6athews ;.'/ub6ed( ')3( -ndoleamine 2,)7dio$ygenase activity and ;7tryptophan transport in human breast cancer cells. Travers 6T, :ow -., Barber 64, Thomson C, Shennan #B.'/ub6ed( ') ( RSubstance isolated from the kelp rhi5oid identified as ;7tryptophan shows high inhibition of breast cancerS.RArticle in CapaneseS by Takahashi >, ?jika 6, #ogasaki 4, >ishi5awa 6, .ukuoka 9, Sahara 9, Sato >, 6ori 6, =ikuchi =.'/ub6ed( ')2( 4apsaicin causes cell7cycle arrest and apoptosis in &<7positive and 7negative breast cancer cells by modulating the &:.<!9&<72 pathway by Thoennissen >9, ?I=elly C, ;u #, -wanski :B, ;a #T, Abbassi S, ;eiter A, =arlan B, 6ehta <, =oeffler 9/.'/ub6ed( '))( 4apsaicin7induced apoptosis in human breast cancer 64.71 cells through caspase7independent pathway by 4hou 44, %u E4, %ang E., 4hou 6C, =uo SC, 4hen #<.'/ub6ed( ')*( Apoptosis induction by dohevanil, a #9A substitutive analog of capsaicin, in 64.71 cells by Tuoya, Baba >, Shimoishi E, 6urata E, Tada 6, =oseki 6, Takahata =.'/ub6ed( ')+( .ruit and vegetable intake in relation to risk of breast cancer in the Black %omenIs 9ealth Study. by Boggs #A, /almer C<, %ise ;A, Spiegelman #, Stampfer 6C, Adams74ampbell ;;, <osenberg ;.'/ub6ed( '),( The antio$idant and anticancer effects of wild carrot oil e$tract by Shebaby %>, &l7Sibai 6, Smith =B, =aram 64, 6roueh 6, #aher 4.. '/ub6ed( ')1( &$tracts from black carrot tissue culture as potent anticancer agents by Sevimli7:ur 4, 4etin B, Akay S, :ulce7-5 S, Eesil74eliktas ?.'/ub6ed( ')"( Selective Anti7/roliferation of 9&<27/ositive Breast 4ancer 4ells by Anthocyanins -dentified by 9igh7Throughput Screening by ;iu %, 8u C, %u S, ;iu E, Eu 8, 4hen C, Tang 8, %ang N, Nhu 8, ;i 8.'/ub6ed( ')2( Tricin *I7?7'erythro7D7guaiacylglyceryl( ether and tricin *I7?7'threo7D7

guaiacylglyceryl( ether isolated from >javara '?ry5a sativa ;. var. >javara(, induce apoptosis in multiple tumor cells by mitochondrial pathway by 6ohanlal S, 6aney S=, Santhoshkumar T<, Cayalekshmy A.'/ub6ed( '*3( %hole Blueberry /owder -nhibits 6etastasis of Triple >egative Breast 4ancer in a 8enograft 6ouse 6odel Through 6odulation of -nflammatory 4ytokines, by =anaya >, Adams ;, Takasaki A, 4hen S.'/ub6ed( '* ( 4hemopreventive and therapeutic activity of dietary blueberry against estrogen7mediated breast cancer by Ceyabalan C, ABil ., 6unagala <, Annamalai ;, 0adhanam 60, :upta <4.'/ub6ed( '*2( Blueberry anthocyanins and pyruvic acid adductsJ anticancer properties in breast cancer cell lines by .aria A, /estana #, Tei$eira #, de .reitas 0, 6ateus >, 4alhau 4.'/ub6ed( '*)( Synthesis and in vitro evaluation of analogues of avocado7produced to$in '@(7'<(7persin in human breast cancer cells by Brooke #:, Shelley &C, <oberts 4:, #enny %A, Sutherland <;, Butt AC.'/ub6ed( '**( A novel plant to$in, persin, with in vivo activity in the mammary gland, induces Bim7dependent apoptosis in human breast cancer cells by Butt AC, <oberts 4:, Seawright AA, ?elrichs /B, 6acleod C=, ;iaw TE, =avallaris 6, Somers7&dgar TC, ;ehrbach :6, %atts 4=, Sutherland <;.'/ub6ed( '*+( Synergistic cytoto$icity between tamo$ifen and the plant to$in persin in human breast cancer cells is dependent on Bim e$pression and mediated by modulation of ceramide metabolism by <oberts 4:, :urisik &, Biden TC, Sutherland <;, Butt AC.'/ub6ed( '*,( &$tracts of strawberry fruits induce intrinsic pathway of apoptosis in breast cancer cells and inhibits tumor progression in mice by Somasagara <<, 9egde 6, 4hiruvella ==, 6usini A, 4houdhary B, <aghavan S4. '/ub6ed( '*1( Strawberry polyphenols are eBually cytoto$ic to tumourigenic and normal human breast and prostate cell lines by %eaver C, Briscoe T, 9ou 6, :oodman 4, =ata S, <oss 9, 6c#ougall :, Stewart #, <iches A.'/ub6ed( '*"( Anticarcinogenic Activity of Strawberry, Blueberry, and <aspberry &$tracts to Breast and 4ervical 4ancer 4ells, by %edge #&, 6eepagala =6, 6agee CB, Smith S9, 9uang :, ;arcom ;;.'/ub6ed( '*2( Anticancer activities of pomegranate e$tracts and genistein in human breast cancer cells by Ceune 6A, =umi7#iaka C, Brown C.'/ubv6ed( '+3( Antiproliferative effects of pomegranate e$tract in 64.71 breast cancer cells are associated with reduced #>A repair gene e$pression and induction of double strand breaks by Shirode AB, =ovvuru /, 4hittur S0, 9enning S6, 9eber #, <eliene <.'/ub6ed( '+ ( /omegranate fruit e$tract impairs invasion and motility in human breast

cancer by =han :>, :orin 6A, <osenthal #, /an H, Bao ;%, %u N., >ewman <A, /awlus A#, Eang /, ;ansky &/, 6erajver S#.'/ub6ed( '+2( The effect of grapefruit intake on endogenous serum estrogen levels in postmenopausal women by 6onroe =<, Stanc5yk .N, BesinBue =9, /ike 64.'/ub6ed( '+)( 9S7 12), a resveratrol analogue, induces cell cycle arrest and apoptotic cell death in human breast cancer cells by =im CA, =im #9, 9ossain 6A, =im 6E, Sung B, Eoon C9, Suh 9, Ceong T4, 4hung 9E, =im >#. '/ub6ed( '+*( :rape polyphenols inhibit Akt!mammalian target of rapamycin signaling and potentiate the effects of gefitinib in breast cancer by 4astillo7 /ichardo ;, #harmawardhane S..'/ub6ed( '++( Suppression of oncoprotein 9er72 and #>A damage after treatment with .lavan7)7 ol vitis labrusca e$tract by Scola :, .ernandes 4orreia ;aurino 44, 6enin &, Salvador 6.'/ub6ed( '+,( Bromelain7induced apoptosis in :-7 3 A breast cancer cells by #handayuthapani S, /ere5 9#, /aroulek A, 4hinnakkannu /, =andalam M, Caffe 6, <athinavelu A.'/ub6ed( '+1( &ffects of oral bromelain administration on the impaired immunocytoto$icity of mononuclear cells from mammary tumor patients by &ckert =, :rabowska &, Stange <, Schneider M, &schmann =, 6aurer 9<. '/ub6ed( '+"( Apple phytochemical e$tracts inhibit proliferation of estrogen7 dependent and estrogen7independent human breast cancer cells through cell cycle modulation by Sun C, ;iu <9.'/ub6ed( '+2( Antiproliferative effects of apple peel e$tract against cancer cells by <eagan7Shaw S, &ggert #, 6ukhtar 9, Ahmad >.'/ub6ed( ',3( Synergistic effect of apple e$tracts and Buercetin )7beta7d7glucoside combination on antiproliferative activity in 64.71 human breast cancer cells in vitro by Eang C, ;iu <9.'/ub6ed( ', ( Apoptosis7inducing activity of hydro$ylated polymetho$yflavones and polymetho$yflavones from orange peel in human breast cancer cells by Sergeev ->, 9o 4T, ;i S, 4olby C, #ushenkov S.'/ub6ed( ',2( 6onoterpenes in breast cancer chemoprevention by 4rowell /;. '/ub6ed( ',)( logical effects of green tea capsule supplementation in pre7surgery postmenopausal breast cancer patients by Eu SS, Spicer #0, 9awes #, Tseng 44, Eang 4S, /ike 64, %u A9'/ub6ed( ',*( &pigenetic effects of green tea polyphenols in cancer by 9enning S6, %ang /, 4arpenter 4;, 9eber #.'/ub6ed(

',+( :reen Tea 4atechinsJ /roposed 6echanisms of Action in Breast 4ancer .ocusing on The -nterplay Between Survival and Apoptosis by Eiannakopoulou &4.'/ub6ed( ',,(&pigallocatechin7)7gallate inhibits stem7like inflammatory breast cancer cells by 6ineva >#, /aulson =&, >aber S/, Eee AS, Sonenshein :&. '/ub6ed( ',1( &pigallocatechin7)7:allate '&:4:( inhibits cell proliferation and migratory behaviour of triple negative breast cancer cells by Braicu 4, :herman 4#, -rimie A, Berindan7>eagoe -.'/ub6ed( ',"( -nhibitory effects and molecular mechanisms of selenium7containing tea polysaccharides on human breast cancer 64.71 cells by 9e >, Shi 8, Nhao E, Tian ;, %ang #, Eang 8.'/ub6ed( ',2( The effects of green tea consumption on incidence of breast cancer and recurrence of breast cancerJ a systematic review and meta7analysis by Seely #, 6ills &C, %u /, 0erma S, :uyatt :9.'/ub6ed( '13( The red wine phenolics piceatannol and myricetin act as agonists for estrogen receptor alpha in human breast cancer cells by 6aggiolini 6, <ecchia A:, Bonofiglio #, 4atalano S, 0ivacBua A, 4arpino A, <ago 0, <ossi <, AndV S.'/ub6ed( '1 ( 4atechin hydrate suppresses 64.71 proliferation through T/+)!4aspase7mediated apoptosis. by Alshatwi AA.'/ub6ed( '12( -nhibition of 4aco72 colon, 64.71 and 9s+1"T breast, and #M *+ prostatic cancer cell proliferation by water7soluble black bean condensed tannins by Bawadi 9A, Bansode <<, Trappey A 2nd, Trua$ <&, ;osso C>. '/ub6ed( '1)( /hytochemicals of black bean seed coatsJ isolation, structure elucidation, and their antiproliferative and antio$idative activities by #ong 6, 9e 8, ;iu <9.'/ub6ed( '1*( -nflammation7related signaling pathways implicating T:.D are revealed in the e$pression profiling of 64.1 cell treated with fermented soybean, chungkookjang by 9wang CS, Eoo 9C, Song 9C, =im ==, 4hun EC, 6atsui T, =im 9B.'/ub6ed( '1+( A soy7based product fermented by &nterococcus faecium and ;actobacillus helveticus inhibits the development of murine breast adenocarcinoma by =inouchi .;, 6aia #4, de Abreu <ibeiro ;4, /laceres 64, de 0alde5 :., 4olombo ;;, <ossi &A, 4arlos -N.'/ub6ed( '1,( /eanut agglutinin inhibits proliferation of cultured breast cancer cells by 6arth 4, #a$enbichler :.'/ub6ed( '11( The influence of dietary lectins on the cell proliferation of human breast cancer cell lines in vitro by 0alentiner M, .abian S, Schumacher M, ;eathem

AC.'/ub6ed( '1"( beta7Sitosterol activates .as signaling in human breast cancer cells by Awad AB, 4hinnam 6, .ink 4S, Bradford /:.'/ub6ed( '12( #ietary fla$seed7trastu5umab interactive effects on the growth of 9&<27overe$pressing human breast tumors 'BT7*1*( by 6ason C=, .u 69, 4hen C, Eu N, Thompson ;M.'/ub6ed( '"3( #ietary fla$seed lignan or oil combined with tamo$ifen treatment affects 64.71 tumor growth through estrogen receptor7 and growth factor7 signaling pathways by Saggar C=, 4hen C, 4orey /, Thompson ;M. '/ub6ed( '" (4onsumption of fla$seed, a rich source of lignans, is associated with reduced breast cancer risk by ;owcock &4, 4otterchio 6, Boucher BA. '/ub6ed( II. In Herbs 1oints 3f View &pidemiological studies. linking herbal medicine in reduced risk of breast cancer have produced inconstant results. -t may be caused by agendas of the originated sources, length of time or following guide lines loosely. Breast cancer widespread in women in Southeast Asian as a result of over 2 decades of economic prosperity has caused major concerns in the governments and scientific communities. &merged suggestions in searching effective treatments in herbal medicine are ongoing, but discover an effective prevention and treatment with little or no side effects has proven difficult. According to statistic, one in " women will be diagnosed to carry some breast cancer tissues sometimes in their life time. #etections of tumor genesis through self observation are still the best approach to cure breast cancer in early stage but reduction of the mortality has not been accounted even with e$tensively modern technology in the field of diagnosis as well as insurance protection in %estern world, needless to say of counties which have little. Breast cancer #mali"nant breast neo$lasm7 is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts '#uctal carcinoma( or the lobules ';obular carcinoma( that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. 0. Anise Anise is a flowering plant of the species of /impinella anisum, genus /impinella, belonging to the family Apiaceae native to to &gypt and the 6editerranean region. The popular herb has been used in traditional herbal medicine as fragrance in soaps, oils, and mouth fresheners and stomachic,

anti7septic, anti7spasmodic, carminative, digestive, e$pectorant, stimulant and tonic agent and to treat head7lice, mites, increase blood pressure, prevent formation of gas in the gastrointestinal tract and menstrual cramps, etc. Anethole, a major chemical compound in Anise, in 6TT and colony formation assays, showed to e$hibit anti &<@ and &< breast cancer through suppression of cell survival to cell proliferation and induction of apoptosis in 64.71 and 6#A76B72) at an optimal concentration of G 3'7)(6 by activating immune response in tumor inhibition' (. &po$ypseudoisoeugenol7 27methyl butyrate isolated from /impinella corymbosa, inhibited the proliferation of both 64.71 and BT7+*2 cells by blocking >.7kappaB'in inflammation, immunity, cell proliferation and apoptosis( transcriptional activity through induced cell cycle arrest in :' (!:'3('4ell cycle( phase and apoptosis'2(. Also in the study of selective estrogen receptor modulators or S&<6s, /impinella anisum in a series of in vitro, e$hibited antiestrogenic effect on breast cancer cells of 64.71')(. %. B rdoc/ B rdoc/ is plant in the group of biennial thistles, genus Arctium, belonging to the family Asteraceae, native to the &uro. -t has been used over thousand of years in 4hina and other traditional herbal medicine as a diuretic, diaphoretic, and a blood purifying agent and to treat wounds and infections stomach ulcers and other digestive problems. ;ignin, a chemical constituent in burdock inhibited 6#A76B72) cell growth by inducing apoptosis through the cell cycle and cell proliferation '<?S!p)" 6A/=( pathway and up regulation of 'regulator proteins that regulate cell death( Bcl72 by enhancing antibody antigens'*(. Also, in Arctiin in Burdock inhibited the growth of breast caner cells through down7 regulation of cell cycle progression cyclin # protein e$pression'+(. Actiin metabolites found in Burdock in the study by the .ourth 6ilitary 6edical Mniversity, in 4hina, showed an inhibited activity on estradiol7mediated proliferation of 64.71 cells at a concentration of 3 micro6',(. ). Cascara sa"rada Cascara sa"rada is a species of buckthorn, genus <hamnus, belonging to the family <hamnaceae, native to western >orth America, itIs bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a la$ative and natural cleansing, etc.. &modin, a chemical compound in 4ascara sagrada, showed to reverse the multi7drug resistance in 64.71!Adr cells and down7regulate &<44 'the

repair of #>A( protein e$pression'1( and suppress the proliferation of B4ap7)1 cells, through the decreased Bcl72 level'regulate cell death(, or induced apoptosis of breast cancer cells by increased e$pression Ba$'involved in p+)7mediated apoptosis( and cytosolic'liBuid found inside cells( cytochrome c'/rotein in the inner membrane of mitochondrial((, on a concentration7and time7dependent manner'"(, or through disruption 'Bad translocation( of the mitochondrial signaling pathway in B4ap7)1 cells'2(. (. & rmeric & rmeric is a perennial plant in the genus 4urcuma, belonging to the family Ningiberaceae, native to tropical South Asia. The herb has been used in traditional medicine as anti7o$idant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, ec5ema, inflammations, etc. 4urcumin a common spice and the well7known chemopreventive agent in Turmeric, inhibited the level of telomerase gene e$pression'produces vulnerability of cancer cells( in breast cells treated' 3(. -ts synthetic version, an ortho7hydro$y substituted analog of curcumin 'B#647A( inhibited 64.71 at a dose eBuivalent to that of curcumin ')3L6( on the modulation of selective anti tumorenegtic markers 'intrinsic pathwayJ p+), Bcl72, Ba$, cyt c, Apaf7 , caspase72, ), /A</W e$trinsic pathwayJ .as;, caspase "( and <?S 'reactive o$ygen species( mediation' (. -n 6#A76B7 2) and BT7*") breast cancer cells, curcumin e$hibited the anti7 proliferation effect, through lowering the e$pression of cyclin # 'involved in regulating cell cycle progression( and 66/ m<>A'involved in the breakdown of e$tracellular matri$ in normal physiological processes and disease processes(' 2(. *. Basil Basil is a species of ?cimum basilicumm, belonging to the family ;amiaceae. -t has been used in traditional medicine to treat cold and flu, coughing, calming the stomach, headache, etc.. 9ydrophobic and hydrophilic fractions '9B and 9;( in Basil, e$hibited anti tumor growth by decreased in basement membrane disintegration, angiogenesis and 66/72 and 66/72 activities in in multiple stages of cancer progression' )(.ABueous ?: leaf e$tract in other study, inhibited proliferation, migration, anchorage independent growth, )# growth and morphogenesis'the biological process of breast cancer( and induction of 4?872 protein'overe$pression in breast cancer cells results in increased cell motility and invasion( in breast cancer cells' *(.

,. )reen &ea :reen tea contains more amount of antio$idants than any drinks or food with the same volume, and is the leaves of 4amellia sinensis, undergone minimal o$idation during processing, originated from 4hina. :reen tea has been a precious drink in traditional 4hinese culture and used e$ceptional in sociali5ation for more than *333 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world. 6ushoom :. lucidum e$tract ':;&( has been used for the promotion of health, longevity and treatment of cancer. 4ombination of green tea ':T&( enhanced the effect of :. lucidum e$tract ':;&( in anti breast cancer cells proliferation 'anchorage7dependent growth( through the down7regulation of e$pression of oncogene c7myc 'freBuently altered in human cancers( in 6#A76B72) cells' +(. -n green tea polyphenols ':T/s(, epigallocatechin7 )7gallate '&:4:( induced apoptosis, cell cycle arrest and suppression of metastasis in tumor cells' ,(. Mnfortunately, in the study of :reen tea consumption and breast caner risk in Capanese women, showed that a green tea consumption is not associated with a decreased risk of breast cancer' 1(. -. 4ed clo!er 4ed Clo!er is a short7lived perennial plant, in the genus Trifolium, belonging to the family .abaceae, native to to &urope, %estern Asia and northwest Africa. The herb has been used in traditional medicine as diuretic and liver cleansing agent and to treat cancer, whooping cough, respiratory problems, and skin inflammations, etc. .ormononetin, a major compound in <ed clover, inactivated -:. !-:. <7 /-)=!Akt 'tumorenegtic( pathways and decreased cyclin # m<>A'regulating cell cycle progression( and protein e$pression in human breast cancer cells in vitro and in vivo' "( and through <as inhibited p)"6A/= pathway' 2(. Mnfortunately, in the study of Soy, red clover, and isoflavones and breast cancer, suggest that red clover may not possess breast cancer7promoting effects'23(. .. Blac/ cohosh Black cohosh 'known as both Actaea racemosa and 4imicifuga racemosa(, a member of is a perennial plant, belonging to the family buttercup, native to >orth America. The herb has been used in herbal medicine to treat symptoms of menopause, premenstrual syndrome '/6S(, painful menstruation, acne, osteoporosis, and for starting labor in pregnant women.

Triterpene glycoside actein from black cohoch showed to inhibit the growth of human breast cancer cells and induced a dose dependent release of calcium into the cytoplasm'fluid protoplasm( by altering the activity of the &< -/)'messenger( receptor and >a,=7AT/ase'en5yme pumps sodium out of cells('2 (. -n .emale Sprague7#awley rats treated with an e$tract of black cohosh enriched in triterpene glycosides '21A(, showed an inhibition of fibroadenomas by reduced =i7,1 and cyclin # protein e$pression.'22(. 2. 8chinacea 8nchinanea also known as purple coneflowers, is a flowering plant of the genus &nchinanea, belonging to the family Asteraceae, native to eastern and central >orth America. The herb has been used in traditional and herbal medicine to treat or prevent colds, flu, infections by stimulating the immune function, etc.. 4ynarine, a chemical compound in &nchinanen affected cell proliferation on 9e;a cells and antiproliferative activity on 64.71 cells'2)(. 09. 1arsley /arsley '/etroselinum crispum( is a biennial flowering plant, genus /etroselinum, belonging to the family Apiaceae, native to the 6editerranean region of southern &urope. The herb has been used in traditional medicine as diuretic agent, and to release spasms, reduce inflammation, clear to$ins, enhance the digestion and stimulate uterus, regulate menstrual cycle, treat edema, etc.. /arley alcoholic seed e$tract '/SA( and seed oil '/S?( of /etroselinum sativum significantly reduced cell viability, and altered the cellular morphology of 64.71 cells in a concentration dependent manner'2*(. 4arnosol found in parsley, and others herbs such as rosemary, sage, targeted multiple deregulated pathways associated with inflammation and cancer'2+(. 00. 4osemary 4osemary is a perennial herb with fragrant, evergreen, needle7like leaves, the genus <osmarinus, belonging to the family ;amiaceae. -ts fresh and dried leaves has been used freBuently in traditional 6editerranean cuisine and as flavor foods while barbecuing. <osemary has been used in traditional medicine as an antiseptic, antio$idant, and antispasmodic agent to treat circulatory problem, ec5ema, rheumatism, muscle pain, etc. 4arnosic acid isolated from <osemary, showed to inhibit proliferation of &<7negative human breast cancer cells and induces : cell cycle arrest'2,(.

?ther in the study of rosemary e$tract, carnosol, carnosic acid, ursolic acid, and rosmarinic acid suppressed the development of tumors in several organs including breasts'21(. -n 6#A76B72) , <osmarinus officinalis had superior antiproliferative effect without induced to$icity'2"(. 0%. 1e$$ermint 1e$$ermint is a hybrid mint with small purple or white flowers and downy leaves, in the genus 6entha, belonging to the family ;amiaceae, native to to &urope. The herb has been used in folk medicine as analgesic, antiseptic, antispasmodic, decongestant, agent and to relieve gas, nausea, and stomach pain due to an irritable bowel, intestinal cramps, or indigestion, infecttion, etc. #ried aBueous e$tractsform 6entha piperita '&$6p( showed cytoto$icity, against 64.71 with the least to$icity'22(. 0'. &hyme Thyme is a genus of Thymus, belonging to the family ;amiaceae, native to &urope and >orth Africa. The herb has been used in flok nedicine to treat bronchitis, whooping cough, sore throat, colic, arthritis, upset stomach, stomach pain 'gastritis(, diarrhea, bedwetting, etc.. Thyme e$tract e$hibited significant cytoto$icity and apoptosis in breast cancer cells '64.71 and 6#A76B72) (')3(') (. -n the study in comparison of some herbs for their effects in human prostate carcinoma cell '/47)(, human lung carcinoma 'A+*2( and human breast cancer '64.71( cell lines, thyme essential oil e$hibited the strongest cytoto$icity towards the above three human cancer cells')2(. 0(. )arlic )arlic #Alli m sati! m7 is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia. -t has been used popularly in traditional and 4hinese medicine in treating common cold and flu to the /lague, blood pressure cholesterol levels, natural antibiotic, etc.. -n a case7control study of )*+ patients with dietary history Buestionnaire consisted of a self7administered food freBuency Buestionnaire, showed breast cancer risk was shown to decrease as increased consumption of garlic and onions'))(. -n breast cancer cells 64.71 and 64.71'ras(, aged garlic e$tract 'A:&( and two of its components, S7allylcysteine 'SA4(, and S7 allyl7mercaptocysteine 'SA64( showed anti7proliferative response due to the alteration in glutathione'antio$idants( level without significant concurrent changes in the glutathione metaboli5ing en5ymes')*(. -n a

breast7cancer cell line '64.71(, #iallyl disulphide '#A#S(, a chemical component in garlic, induced phosphatidylserine translocation from the inner to the outer leaflet of the plasma membrane and activates caspase'mechanisms of apoptosis(7). #A#S also modulated the cellular levels of Ba$, Bcl72, Bcl7$;, and Bcl7w 'induced apoptosis(, in a dose7 dependent manner')+(. +. )in/"o biloba )in/"o biloba is oldest living tree species, genus :inkgo, belonging to the family :inkgoaceae, native to 4hina, from temperate 5one to subtropical 5one and some parts of north America. -t 9as been used in traditional herbal medicine in treating impotence, memory loss, respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting. :inkgo biloba e$tract ':b&( used conjunction with Tamo$ifen 'TA6( in female Sprague7#awley 'S#( rats, showed a slightly beneficial effect on the therapeutic efficacy of TA6 in female S# breast cancer bearing rats'),(. -n the e$periment of :inkgo biloba e$tract ':B&( effected against 6#A76B7 2) '&<7negative( human breast cancer cell line, showed that cytoto$icity effects of :B& in 6#A76B72) lead to #>A fragmentation at high concentrations '+33 and ,333 Lg!ml(. activated the 4aspase7) and m<>A levels of apoptosis7related genes 'Bcl72 and Ba$(')1(. -n the study of Antiestrogenic activities of e$tract of :inkgo biloba, showed an reduced &2 levels by stimulating the &2 metabolism and inhibiting &2 synthesis.')"(. 0,. 4eishi : shroom 4eishi m shroom or 6in";hi is a fungal species in the genus :anoderma, belonging to the family :anodermataceae, native to Asia. The herb has been use in traditional medicine as anti7caners and anti inflammatory, antio$idant agent and to enhance immune function, treat hepatitis B virus, protect against neuron degeneration, etc.. -n -nflammatory Breast 4ancer '-B4(, with overe$press &7cadherin 'plays an important role in the growth, development and the intercellular adhesion of epithelial cells( and the eukaryotic initiation factor *:- 'e-.*:-('an essential protein that is the target for translational regulation in many cellular processes(, <eishi showed reduced e$pression of &7cadherin, mT?<'cell proliferation(, e-.*:, and p13S,='cell growth and : cell cycle progression( and cell regulation activities'activity of e$tracellular regulated kinase '&<= !2((')2(. -n the study of the same, <eishi showed to inhibited the e$pression of genes involved in cancer cell survival and proliferation

'B4;72, T&<T, /#:.B( of invasion and metastasis breast cancer cells'66/72('*3(. An ethanol7soluble and acidic component '&SA4( prepared from <eishi reduced the cell viability of 64.71 and 6#A76B7 2) cells in a concentration7dependent manner with -4'+3( of about 33 Lg!m; and ,3 Lg!m;, respectively through effectively mediated : cell cycle arrest and e$hibited apoptosis'* (. 0-. )ra$e +eed 85tract )ra$e +eed 85tract is the commercial e$tracts from whole grape seeds that contains many concentrations, including vitamin &, flavonoids, linoleic acid, oligomeric proanthocyanidins'?/4s(, etc..The herb has been used in traditional medicine as antio$idant, anti7inflammatory agents and to treat skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood vessels, lower cholesterol, etc. -n highly metastatic 6#A76B2) breast cancer cell line, grape seed e$tract ':S&(showed the effectiveness in cell proliferation and apoptosis through decreased cell migration and invasion, likely by suppressing the D7 catenin''plays an important role in the growth, development and the intercellular adhesion of epithelial cells( e$pression and locali5ation, fascin'cell motility and migration( and >.7XB''a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis( e$pression'*2(. /roanthocyanidin, other chemical constituent in grape seeds, showed to suppress precancerous cellular carcinogenesis through down regulated gene e$pression of cytochrome7/*+3 en5ymes 4E/ A and 4E/ B 'carcinogenic intermediates('*)(. -n breast cancer cell 64.71, :rape seed e$tract inhibited the proliferation and downregulated the gene e$pression of survivin'baculoviral inhibitor(through through arresting the cell cycle in S phase''synthesis phase for #>A reduplication(('**( 0.. <andelion <andelion is a herbaceous perennial plant, genus Tara$acum, beloning to the family Asteraceae, native to temperate regions of the world. -t has been used in traditional and herbal medicine to treat gout, ec5ema, acne, gall bladder, kidney, liver and urinary disorders, hypoglycemia, dyspepsia with constipation, edema, blood pressure and heart weakness, chronic joint, skin diseases, etc. ABueous e$tracts e$tracts '#<&(, from the mature leaves, flowers and roots of dandelion were investigated for the effects in tumor progression in related processes such as proliferation and invasion, only the crude e$tract of dandelion leaf '#;&( showed to decrease the growth of 64.71!AN breast

cancer cells in an &<='transmits signals from many e$tracellular agents to regulate cellular processes such as proliferation, differentiation and cell cycle progression('*+(7dependent manner'*,(. 02. )insen" :inseng is a slow7growing perennial plants with fleshy roots, the genus /ana$, belonging to the family Araliaceae. #epending to the climate where it grows, ginseng can be classified mainly into /ana$ ginseng Asian ginseng 'root(, <ed ginseng, wild ginseng, American ginseng 'root(. The investigation of :inseng effects in a cohort of ,*++ breast cancer patients recruited to the Shanghai Breast 4ancer Study between August 22, and 6arch 22" in Shanghai, 4hina showed that :inseng use after cancer diagnosis, particularly current use, improved Buality of life and reduced risk of death'*1(. -n breast cancer cell line 64.71 cells, =orean red ginseng '=<:( e$tracts activated the &<F and &<D '&strogen receptor alpha and Beta( through regulating the m<>A levels of estrogen7responsive genes such as pS2 and &S< to decreased the protein level of &<F. Also :insenoside from /ana$ notoginseng decreased the survival of breast cancer cells by induction of apoptosis and : 'cell cycle( phase arrest and inhibited the growth of breast cancer $enografts'a graft obtained from breast cancer cells of one species and transplanted to a member of another species( in vivo'*2( and inhibited 6#62'an oncoprotein that controls tumorigenesis( e$pression at both transcriptional'gene e$pression at the <>A7 and post7translational levels in human breast cancer cells with various p+)'cellular tumor antigen( statuses'*2(. %9. Hawthorn Hawthorn is a shrubs and trees of the genus 4rataegus, belonging to the family <osaceae, native to temperate regions of the >orthern 9emisphere in &urope, Asia and >orth America. The herb has been used in traditional medicine to treat heart disease and symptoms of heart diseases such as irregular heartbeat, high blood pressure, chest pain, hardening of the arteries, etc., circulatory disorders and respiratory illnesses. -n in human 64.71 breast carcinoma cells, peel polyphenolic e$tract '9//( and flesh polyphenolic e$tract '9./( from hawthorn fruit although 9// was more effective against 64.71 cells than 9./, both 9// and 9./ interfereed the cell7cycle arrest at the S7phase, and also dose7 dependently led to apoptosis of 64.71 cells via the mitochondrial pathway'inner mitochondrial membrane(, by the mechanism of apoptosis of caspase7) and caspase72 and the elevation of intracellular

<?S'reactive o$ygen species( production'+3(. %0. 6icorice #)lycyrrhi;a )labra7 6icorice #)lycyrrhi;a )labra7 is also known as sweetwood, a genus :lycyrrhi5a, belonging to the family .abaceae, native to the 6editerranean and certain areas of Asia. The herb has been used in traditional medicine to treat skin diseases, coughs, constipation, bronchitis, inflammation, arthritis, etc.. -soliBuiritigenin, a flavonoid phytoestrogen from licorice, induced growth inhibition and apoptosis through downregulating multiple key en5ymes in AA metabolic network'inflammatory mediators( and the deactivation of anti7apoptosis and increased cell proliferation'/-)=!Akt( in human breast cancer'+ (. ;icochalcone & ';ic&(, other phenolic constituent of licorice, in 6#A76B72) cells inhibited cell migration and invasion and downregulated the e$pression of proliferative and anti apoptotic pathways and unregulated secretion of cell proliferation inhibitor'+2(. &thanol e$tract of roasted licorice 'r;&( found to be effective in inhibition of breast cancer7mediated bone destruction by suppressing receptor activator of nuclear factor XB ligand '<A>=;(7induced osteoclast formation in B66s'bone marrow7derived macrophages 'B66s('+)(. %%, 3re"ano ?regano is a perennial herb with aromatic and balsamic flavor, of the genus ?riganum in the family ;amiaceae, native to western and southwestern &urasia and the 6editerranean. The herb has been used in traditional medicine as anti7bacterial, anti7fungal, and anti7viral agent and to treat skin burns, cuts and bruises, sore throat, asthma, colds, coughs and flu, etc. 4arvacrol, a chemical constituent in ?regano showed the anti7tumor effects on human metastatic breast cancer cells, 6#A76B 2) through down regulated the function of mitochondrial membrane potential of the cells'+*(. -n breast cancer cell lines 64.71, 6#A76B7*," and 6#A76B72) , ?riganum acutidens '?A( e$tracts showed cytoto$icity on all ) cancer cell lines through e$pression of Anne$in7positive cells level in ?A7treated cell lines and caspase71 'transduction pathways of apoptosis, necrosis and inflammation( protein and TM>&;7positive 'indication of apoptosis and accidental cell death( cells'++(. -n the investigation of essential oil from oregano leaves '?riganum compactum(, showed that ethyl acetate e$tract ')3 mg!;( and ethanol e$tract '+, mg!;( are effective in ambition against human breast cancer cells '64.1('+,(.

2). 4h barb 4h barb is a small flower grouped with large compound leafy in the the genus <heum, belonging to the family /olygonaceae. The herb has been used in traditional medicine as la$ative agent, reduce inflammation and treat diarrhea, dysentery blood clots, tumor red and painful eyes abdominal7 distention and!or pain blood in stool hemorrhoidal bleeding urinationJ burning sensation, absence of menses, etc. AnthraBuinones emodin and aloe7emodin chemical constituents in rhubarb, both inhibited breast cancer cell proliferation by downregulating &< F protein levels in suppressing &< F transcriptional activation'+1(. Study of combined curcumin and emodin administration showed the inhibition of proliferation '6TT assay(, survival 'flow cytometry(, and invasion 'transwell migration assay( of breast cancer cells'+"(. <hein, a anthraBuinone derivatives, showed antiproliferative and apoptotic effects on both 9&<27overe$pressing 64.71 '64.71!9&<2( and control vector 64.71 '64.71!0&4( cells'+2(. %(. Cat=s claw Cat=s claw found in in the tropical jungles of South and 4entral America, is a genus Mncaria, belonging to the family <ubiaceae. -t has been used in traditional medicine over two thousand years as a tonic, contraceptive, anti7 inflammatory and infectious agent, and to treat diarrhea, rheumatic disorders, acne, diabetes, cancer and diseases of the urinary tract, etc.. &$tracts and chromatographic fractions of the 4atIs claw, e$erted a direct antiproliferative activity on 64.1, with an -4+3 of 3 mg!ml and 23 mg!ml, respectively.,3(. Also, pentacyclic o$indole alkaloid mitraphylline isolated from Mncaria tomentosa bark, using cyclophosphamide and vincristine as reference controls, showed to inhibit the growth of both human sarcoma and breast cancer cell lines in a dose7dependent manner',3(. &pidemiologically, the list above has been proven to be effective in reducing risk and treatment of breast cancer through lowering the gene e$pression of protein in mitochondrial activation of proliferative and anti apoptotic, down regulating tumorgenic and up regulating anticancer pathways. ?nce again, please consult your herbal specialist before applying and inform your doctor, if you are currently taking any prescribed medicine. Chinese +ecrets &o Fatty 6i!er And 3besity 4e!ersal Mse The <evolutionary .indings To Achieve ?ptimal 9ealth And ;oose %eight

+&31 HAI4 63++ > 184:AN8N&6? .ill in Bald Spots, Stop Thinning 9air And <estore <eceding 9air ;ines, >aturally 4eferences ' ( Anethole suppressed cell survival and induced apoptosis in human breast cancer cells independent of estrogen receptor status by 4hen 49, de:raffenried ;A.'/ub6ed( '2( -nhibition of >.7kappaB7mediated transcription and induction of apoptosis in human breast cancer cells by epo$ypseudoisoeugenol727methyl butyrate by 6a :, Tabanca >, 9usnu 4an Baser =, =irimer >, /asco #S, =han -A, =han S-.'/ub6ed( ')( :reek plant e$tracts e$hibit selective estrogen receptor modulator 'S&<6(7like properties by =assi &, /apoutsi N, .okialakis >, 6essari -, 6itakou S, 6outsatsou /.'/ub6ed( '*( Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor7negative breast cancer cells through the <?S!p)" 6A/= pathway and epigenetic regulation by 9sieh 4C , =uo /;2, 9su E4), 9uang E.*, Tsai &6+, 9su E;,.'/ub6ed( '+( <?S7activated p)" 6A/=!&<=7Akt cascade plays a central role in palmitic acid7stimulated hepatocyte proliferation by 6atsu5aki E, =oyama 6, 9itomi T, Eokota T, =awanaka 6, >ishikawa A, :ermain #, Sakai T. '/ub6ed( ',( <?S7activated p)" 6A/=!&<=7Akt cascade plays a central role in palmitic acid7stimulated hepatocyte proliferation by 8ie ;9, Ahn &6, Akao T, Abdel79afe5 AA, >akamura >, 9attori 6.'/ub6ed( '1( &modin affects &<44 e$pression in breast cancer cells by .u C6, Nhou C, Shi C, 8ie CS, 9uang ;, Eip AE, ;oo %T, 4how ;%, >g &;.'/ub6ed( '"( &modin7induced apoptosis in human breast cancer B4ap7)1 cells through the mitochondrial signaling pathway by 9uang N, 4hen :, Shi /. '/ub6ed( '2( &ffects of emodin on the gene e$pression profiling of human breast carcinoma cells by 9uang N, 4hen :, Shi /.'/ub6ed( ' 3( 4omparison of inhibitory effect of curcumin nanoparticles and free curcumin in human telomerase reverse transcriptase gene e$pression in breast cancer by =a5emi7;omedasht ., <ami A, Narghami >.'/ub6ed( ' ( 6echanism of apoptotic induction in human breast cancer cell, 64.71, by an analog of curcumin in comparison with curcumin 7 An in vitro and in silico approach by 6ohankumar = , /ajaniradje S , Sridharan S , Singh

0=2, <onsard ;), Banerjea A4), Benson 4S*, 4oumar 6S2, <ajagopalan <'/ub6ed( ' 2( 4urcumin inhibits cell proliferation of 6#A76B72) and BT7*") breast cancer cells mediated by down7regulation of >.kappaB, cyclin# and 66/7 transcription by ;iu H, ;oo %T, S5e S4, Tong E.'/ub6ed( ' )( ?cimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matri$ metalloproteases by >angia76akker /, <a5 T, Tait ;, Shekhar 6/, ;i 9, Balan 0, 6akker 9, .ridman <, 6addipati =, <a5 A.'/ub6ed( ' *( -nhibition of breast tumor growth and angiogenesis by a medicinal herbJ ?cimum gratissimum by >angia76akker /, Tait ;, Shekhar 6/, /alomino &, 9ogan 0, /iechocki 6/, .unasaka T, <a5 A'/ub6ed( ' +( 4ombined effect of green tea and :anoderma lucidum on invasive behavior of breast cancer cells by Thyagarajan A, Nhu C, Sliva #.'/ub6ed( ' ,(#ownstream 4arcinogenesis Signaling /athways by :reen Tea /olyphenolsJ A Translational /erspective of 4hemoprevention and Treatment for 4ancers by 9u :, Nhang ;, <ong E, >i 8, Sun E.'/ub6ed( ' 1( :reen tea consumption and breast cancer risk in Capanese womenJ a case7control study by -wasaki 6, 6i5usawa C, =asuga E, Eokoyama S, ?numa 9, >ishimura 9, =usama <, Tsugane S.'/ub6ed( ' "( .ormononetin induces cell cycle arrest of human breast cancer cells via -:. !/-)=!Akt pathways in vitro and in vivo by 4hen C, Neng C, 8in 6, 9uang %, 4hen 8.'/ub6ed( ' 2(.ormononetin7induced apoptosis by activation of <as!p)" mitogen7 activated protein kinase in estrogen receptor7positive human breast cancer cells by 4hen C, Sun ;.'/ub6ed( '23( Soy, red clover, and isoflavones and breast cancerJ a systematic review by .rit5 9, Seely #, .lower :, Skidmore B, .ernandes <, 0adeboncoeur S, =ennedy #, 4ooley =, %ong <, Sagar S, Sabri &, .ergusson #.'/ub6ed( '2 ( Actein induces calcium release in human breast cancer cells by &inbond ;S, 6ighty C, <edenti S, %u 9A.'/ub6ed( '22( 4hemopreventive potential of black cohosh on breast cancer in Sprague7#awley rats by &inbond ;S, Soffritti 6, #egli &sposti #, Tibaldi &, ;auriola 6, Bua ;, 9e =, :enovese :, Su T, 9uggins ;, %ang 8, <oller 6, %u 9A.'/ub6ed( '2)( /roliferative activity of &chinacea angustifolia root e$tracts on cancer cellsJ -nterference with do$orubicin cytoto$icity by 9untimer &#, 9alaweish .T, 4hase 44.'/ub6ed( '2*( Anticancer activity of /etroselinum sativum seed e$tracts on 64.71 human breast cancer cells by .arshori >>, Al7Sheddi &S, Al7?Bail 66,

6usarrat C, Al7=hedhairy AA, SiddiBui 6A.'/ub6ed( '2+( 4arnosolJ a promising anti7cancer and anti7inflammatory agent by Cohnson CC.'/ub6ed( '2,( 4arnosic acid inhibits the growth of &<7negative human breast cancer cells and synergi5es with curcumin by &inbond ;S, %u 9A, =ashiwa5aki <, 9e =, <oller 6, Su T, %ang 8, :oldsberry S.'/ub6ed( '21( <osemary and cancer preventionJ preclinical perspectives by >go S>, %illiams #B, 9ead <C.'/ub6ed( '2"( -nhibitory effects of rosemary e$tracts, carnosic acid and rosmarinic acid on the growth of various human cancer cell lines by Eesil74eliktas ?, Sevimli 4, Bedir &, 0ardar7Sukan ..'/ub6ed( '22( 4ytoto$ic impact of phenolics from ;amiaceae species on human breast cancer cells by Berdowska -, NieliYski B, .ecka -, =ulbacka C, Sac5ko C, :amian A.'/ub6ed( ')3( &ffects of Thymus serpyllum e$tract on cell proliferation, apoptosis and epigenetic events in human breast cancer cells by Bo5kurt &, Atmaca 9, =isim A, M5unoglu S, Mslu <, =araca B.'/ub6ed( ') ( 4ytoto$ic impact of phenolics from ;amiaceae species on human breast cancer cells by Berdowska -, NieliYski B, .ecka -, =ulbacka C, Sac5ko C, :amian A.'/ub6ed( ')2( Activities of ten essential oils towards /ropionibacterium acnes and /47 ), A7+*2 and 64.71 cancer cells by Nu E, Eu 9, ;iang ;, .u E, &fferth T, ;iu 8, %u >.'/ub6ed( '))( :arlic, onion and cereal fibre as protective factors for breast cancerJ a .rench case7control study by 4hallier B, /erarnau C6, 0iel C..'/ub6ed( ')*( Antiproliferative effects of garlic constituents in cultured human breast7 cancer cells by ;i :, Hiao 4, ;in <, /into C, ?sborne 6, Tiwari <. '/ub6ed( ')+( #iallyl disulfide7induced apoptosis in a breast7cancer cell line '64.71( may be caused by inhibition of histone deacetylation by Altonsy 6?, 9abib T>, Andrews S4.'/ub6ed( '),( &ffects of :inkgo biloba on chemically7induced mammary tumors in rats receiving tamo$ifen by #ias 64, .urtado =S, <odrigues 6A, Barbisan ;..'/ub6ed( ')1( 4hemopreventive effects of :inkgo biloba e$tract in estrogen7negative human breast cancer cells by /ark EC, =im 6C, =im 9<, Ei 6S, 4hung =9, ?h S6.'/ub6ed( ')"( Antiestrogenic activities of :inkgo biloba e$tracts by ?h S6, 4hung =9.'/ub6ed( ')2( Anti7tumor effects of :anoderma lucidum 'reishi( in inflammatory

breast cancer in in vivo and in vitro models by Suare57Arroyo -C, <osario7 Acevedo <, Aguilar7/ere5 A, 4lemente /;, 4ubano ;A, Serrano C, Schneider <C, 6artZne576ontemayor 66.'/ub6ed( '*3( :anoderma lucidum '<eishi( inhibits cancer cell growth and e$pression of key molecules in inflammatory breast cancer by 6artZne576ontemayor 66, Acevedo <<, ?tero7.ranBui &, 4ubano ;A, #harmawardhane S.. '/ub6ed( '* ( :anoderma lucidum e$tract induces : cell cycle arrest, and apoptosis in human breast cancer cells by %u :, Hian N, :uo C, 9u #, Bao C, 8ie C, 8u %, ;u C, 4hen 8, %ang E.'/ub6ed( '*2(:rape seed e$tract suppresses 6#A76B2) breast cancer cell migration and invasion by #inicola S, /asBualato A, 4ucina A, 4oluccia /, .erranti ., 4anipari <, 4ati5one A, /roietti S, #IAnselmi ., <icci :, /alombo A, Bi55arri 6.'/ub6ed( '*)(:rape seed proanthocyanidin suppression of breast cell carcinogenesis induced by chronic e$posure to combined *7'methylnitrosamino(7 7')7 pyridyl(7 7butanone and ben5oRaSpyrene by Song 8, Siriwardhana >, <athore =, ;in #, %ang 94.'/ub6ed( '**(R:rape seed e$tract inhibit proliferation of breast cancer cell 64.71 and decrease the gene e$pression of survivinS.RArticle in 4hineseS by 4hen 4, ;iu 4, Nhang C, Eang H, Teng ..'/ub6ed( '*+( The e$tracellular signal7regulated kinaseJ multiple substrates regulate diverse cellular functions by Eoon S, Seger <.'/ub6ed( '*,( &valuation of aBueous e$tracts of Tara$acum officinale on growth and invasion of breast and prostate cancer cells by Sigstedt S4, 9ooten 4C, 4allewaert 64, Cenkins A<, <omero A&, /ullin 6C, =ornienko A, ;owrey T=, Slambrouck S0, Steelant %..'/ub6ed( '*1( Association of ginseng use with survival and Buality of life among breast cancer patients by 4ui E, Shu 8?, :ao ET, 4ai 9, Tao 69, Nheng %.'/ub6ed( '*"( &strogen receptor is activated by korean red ginseng in vitro but not in vivo by Shim 6=, ;ee EC.'/ub6ed( '*2(>atural product ginsenoside 2+7?49)7//# inhibits breast cancer growth and metastasis through down7regulating 6#62 by %ang %, Nhang 8, Hin CC, 0oruganti S, >ag SA, %ang 69, %ang 9, Nhang <.'/ub6ed( '+3( #ifferential effects of polyphenols7enriched e$tracts from hawthorn fruit peels and fleshes on cell cycle and apoptosis in human 64.71 breast carcinoma cells by ;i T, Nhu C, :uo ;, Shi 8, ;iu E, Eang 8.'/ub6ed( '+ ( -soliBuiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of

/-)=!Akt in human breast cancer by ;i E, Nhao 9, %ang E, Nheng 9, Eu %, 4hai 9, Nhang C, .alck C<, :uo A6, Eue C, /eng <, Eang C.'/ub6ed( '+2( ;icochalcone & present in licorice suppresses lung metastasis in the *T mammary orthotopic cancer model. by =won SC, /ark SE, =won :T, ;ee =%, =ang E9, 4hoi 6S, Eun C%, Ceon C9, Cun C:, /ark C9.'/ub6ed( '+)(The -nhibitory &ffect of <oasted ;icorice &$tract on 9uman 6etastatic Breast 4ancer 4ell7-nduced Bone #estruction by ;ee S=, /ark ==, /ark C9, ;im SS, 4hung %E.'/ub6ed( '+*(Anti7proliferative effects of carvacrol on a human metastatic breast cancer cell line, 6#A76B 2) by Arunasree =6'/ub6ed( '++( Antitumor effects of ?riganum acutidens e$tracts on human breast cancer by Tuncer &, Mnver7Saraydin S, Tepe B, =aradayi S, ?5er 9, =aradayi =, -nan #, &lago5 S, /olat N, #uman 6, Turan 6.'/ub6ed( '+,(?reganoJ chemical analysis and evaluation of its antimalarial, antio$idant, and cytoto$ic activities by &l Babili ., Bouajila C, Souchard C/, Bertrand 4, Bellvert ., .ouraste -, 6oulis 4, 0alentin A.'/ub6ed(. '+1(&modin and Aloe7&modin Suppress Breast 4ancer 4ell /roliferation through &< F -nhibition by 9uang /9, 9uang 4E, 4hen 64, ;ee ET, Eue 49, %ang 9E, ;in 9.'/ub6ed( '+"( Synergistic effects of curcumin with emodin against the proliferation and invasion of breast cancer cells through upregulation of mi<7)*a by :uo C, ;i %, Shi 9, 8ie 8, ;i ;, Tang 9, %u 6, =ong E, Eang ;, :ao C, ;iu /, %ei %, 8ie 8.'/ub6ed( '+2(<hein induces apoptosis in human breast cancer cells by 4hang 4E, 4han 9;, ;in 9E, %ay T#, =ao 64, Song 6N, ;in EC, ;in 4%.'/ub6ed( ',3(The antiproliferative effects of Mncaria tomentosa e$tracts and fractions on the growth of breast cancer cell line by <iva ;, 4oradini #, #i .ron5o :, #e .eo 0, #e Tommasi >, #e Simone ., /i55a 4'/ub6ed( ',3(4ytoto$ic effect of the pentacyclic o$indole alkaloid mitraphylline isolated from Mncaria tomentosa bark on human &wingIs sarcoma and breast cancer cell lines by :arcZa :im[ne5 #, :arcZa /rado &, STen5 <odrZgue5 T, .ernTnde5 Arche A, #e la /uerta <.'/ub6ed(. III. In Vitamins 1oints of View A. Vitamin A 0itamins form an important part in human diet. &pidemiological studies, linking vitamin A in reduced risk of breast cancer have produced uncleared result' (' a(' b(. But in certain studies, vitamin A in form of retinoids and carotenoids is effective in inhibition of breast cancer cell lines through many anti porfilerative and apoptotic pathways.

Vitamin A is a general term of 0itamin A <etinol, retinal, beta7carotene, alpha7carotene, gamma7carotene, and beta7crypto$anthin best known for its functions for vision health and antio$idant scavenger and essential for growth and differentiation of a number of cells and tissues. <ecommended intakes of vitamin A, according to the -nstitute of 6edicine of the >ational Academies 'formerly >ational Academy of Sciences( is ,33 \g daily as e$tremely high doses ']2333 mg( can be to$icity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc. 0. 4etinols ;ack of the retinoic acid receptor beta '<A< beta( gene e$pression causes of abnormal regulation by retinoic acid '<A( are common features in human lung cancer and breast cancer cells'2( Suggestion of using retinoids, the natural and synthetic vitamin A derivatives in chemoprevention because of its function in modification of abnormal dell growth in 4ancer tissues')( by e$erting anticancer effects through its retinoid receptors, the <A receptors '<A<s( and retinoid 8 receptors '<8<s(in regualating the target gene causes of the diseases'*(. -n S=7B<7) and T*1# human breast cancer cells, retinoid showed to be effectively in regulates mammary epithelial cell growth and differentiation through signaling via retinoic acid '<A( and retinoid 8 receptors '<A<s and <8<s( leading to apoptosis in &<7 S=7B<7) and &<@ T*1# breast cancer cells'+(. All7trans retinoic acid'AT<A(, a synthetic version of vitamin A, showed effectively in inhibition of breast cancer stem cells, >4S4s and 4S4s, through impairment of the self7renewing ability of 4S4s and promotion of 4S4s to differentiate',(. -n human breast cancer cell lines of 6#A76B7*," and 64.71, AT<A inhibited the proliferation and the e$pression of B/ 'e$pression of B/ protein correlated with breast tumor progression and invasion( in breast cancer cells'1(. -n human breast cancer 6#A76B72) cells, the synthetic retinoid *7amino7 27tri7fluoromethyl7phenyl ester 'AT/<( inhibited cells reduced migration and reduced phosphorylation of &<='cellular proliferation, differentiation, and survival(, C>='cellular apoptosis( and p)"'highly e$pressed in aggressive and invasive breast cancers( in breast cancer'"(. <etinoic acid '<A(, a vitamin A metabolite, induced breast cancer cell apoptosis through type - -.> autocrine 'activation of T cells, B cells, and natural killer cells(signaling, caspase7" and caspase7)'4ell apoptosis( activation, as well as T<A-;'induces the process of cell death( signaling'2(. Taking to these

accounts, <etinols may be beneficial as a potent agent in preventing and treating breast cancer. %. Carotenoids#beta>carotene, al$ha>carotene, "amma>carotene and beta>cry$to5anthin7 4arotenoids, plant pigments, converted to vitamin A after intake, though to play an important role in prevention and treatment of some diseases through it antio$idant effects. -n postmenopausal women, dietary beta7carotene intake is found to be effective in reduced risk of breast caner with or without high alcohol intake' (' 2(' )(' ,(. ?ther studies of circulating carotenoids, also showed that high levels of beta carotene circulation are associated to decreased risk of breast cancer' *(. -n the risk of breast cancer by estrogen receptor '&<( and progesterone receptor '/<(, D7carotene intakes were inversely associated with the risk of &<7negative '&<7(but not &<7 positive breast cancer cell lines' +(. -n genetic polymorphisms of >?S), intake of D7carotene modified and protected against risk of breast cancer predominantly in individuals with the T:JT: diplotype of >?S)' 1(. -n related with other supplements, intake of multivitamins including beta7carotene, vitamin 4, vitamin & and 5inc for 3 Eears or more may protect from developing breast cancer in postmenopausal women' "(. biologically, the protection of antio$idants including D7carotene against breast cancer was associated to activation of immune response in the course of the disease' 2(. -n smokers, dietary alpha7carotene and beta7 carotene are associated with reduced risk of breast cancer among women who do not use dietary supplements'23(. -n estrogen receptor '&<( and progesterone receptor '/<( status, intakes of F7carotene was associated with reduced risk of &<7, but not &<@, breast cancer' +(. -n women with high mammographic density, using a computer7 assisted thresholding method, total carotenoids were associated with a +3A reduction in breast cancer risk'2 (. -n a total of 2,2 cases of breast cancer diagnosed after blood draw and prior to Cune , 22", alpha carotene was inversely associated in reduced risk of breast cancer greater for invasive cancers with nodal metastasis'22(. -n invasive breast cancer, high consumption of carotenoids may reduce risk of of breast cancer in premenopausal but not postmenopausal women, particularly among smokers, including alpha7carotene'2)(. -n comparison of blood concentrations of carotenoids and carotenoids assessed by dietary Buestionnaires, showed strong relationship between biomarkers and the reduced risk of breast cancer'2*(. -n breast cancers defined by estrogen

receptor '&<( and progesterone receptor '/<( status, dietary alpha7carotene was inversely associated with risk of &<@/<@breast cancer, but not with other breast cancer groups jointly defined by &< and /< status'2+(. -n the study of gene ?',(7methylguanine #>A methyl7transferase '6:6T( involved in cellular defense against, dietary antio$idants are associated to inversely reduce risk of breast cancer through possible modulation of polymorphisms in 6:6T'2,(. -n malignant melanoma, mammary carcinoma and lung adenocarcinoma cells growth, water and ethanol e$tracts from glaucophyte 4yanophora parado$a '4p( with /heophorbide a, D7crypto$anthin and 5ea$anthin were found to significantly inhibit the growth of the three cancer cell lines mentioned above in vitro, at 33 \g ^ m;..'21(. -n the study of the associations of plasma levels of tocopherols, retinol, carotenoids with the risk of developing breast cancer among 4hinese women, researcers found that high levels of plasma lycopene other than trans, +7 and 17cis or trans alpha7crypto$anthin were inversely associated with the risk of developing breast cancer'2"(. #ietary vitamin A, includes retinol, retinal, retinoic acid, and several provitamin A carotenoids has been found significantly in reduced risk and treatment of breast cancer through modification of malignant cell growth, e$pression of down7regulation of pro proliferative and up7regualtion of apoptotic pathway. <egardless to its anti7breast cancer effects, overdoses can lead to to$ic symptoms. /lease make sure you follow the guideline of the -nstitute of 6edicine of the >ational Academies. 4eferences ' ( 0itamin supplement consumption and breast cancer riskJ a review by 6isotti A6, :nagnarella /.'/ub6ed( ' a( 0itamins 4 and &, retinol, beta7carotene and dietary fibre in relation to breast cancer riskJ a prospective cohort study by 0erhoeven #T, Assen >, :oldbohm <A, #orant &, van It 0eer /, Sturmans ., 9ermus <C, van den Brandt /A.'/ub6ed( ' b(6icronutrient intake and breast cancer characteristics among postmenopausal women by <oswall >, ?lsen A, 4hristensen C, #ragsted ;?, ?vervad =, Tj_nneland A.'/ub6ed( '2( <etinoid receptors in human lung cancer and breast cancer by Nhang 8=, ;iu E, ;ee 6?.'/ub6ed( ')( <etinoids in cancer chemoprevention by ?kuno 6, =ojima S,

6atsushima7>ishiwaki <, Tsurumi 9, 6uto E, .riedman S;, 6oriwaki 9. '/ub6ed( '*( -nhibition of trans7retinoic acid7resistant human breast cancer cell growth by retinoid 8 receptor7selective retinoids by %u H, #awson 6-, Nheng E, 9obbs /#, Agadir A, Cong ;, ;i E, ;iu <, ;in B, Nhang 8=.'/ub6ed( '+( Activation of retinoic acid receptor alpha is sufficient for full induction of retinoid responses in S=7B<7) and T*1# human breast cancer cells by Schneider S6, ?ffterdinger 6, 9uber 9, :runt T%.'/ub6ed( ',( RAll7trans retinoic acid effectively inhibits breast cancer stem cells growth in vitroS. RArticle in 4hineseS by Neng %:, 9u /, %ang C>, ;iu <B.'/ub6ed( '1( R&ffects of all trans retinoic acid on the e$pression alterations of beta7 protein in human breast cancer cell lines of 6#A76B7*," and 64.71S. RArticle in 4hinese by Su C, ;i 6H, Nhong :S.'/ub6ed( '"( A novel all7trans retinoid acid derivatives inhibits the migration of breast cancer cell lines 6#A76B72) via myosin light chain kinase involving p)"76A/= pathway by %ang B, Ean E, Nhou C, Nhou H, :ui S, %ang E. '/ub6ed( '2( Synergy between <A and T;<) promotes type - -.>7dependent apoptosis through upregulation of T<A-; pathway in breast cancer cells by Bernardo A<, 4osgaya C6, Aranda A, Cim[ne57;ara A6.'/ub6ed( ' 3( 4is7retinol dehydrogenaseJ 27cis7retinol metabolism and its effect on proliferation of human 64.1 breast cancer cells by /aik C, Blaner %S, Swisshelm =.'/ub6ed( ' ( #ietary beta7carotene, vitamin 4 and & intake and breast cancer risk in the &uropean /rospective -nvestigation into 4ancer and >utrition '&/-4( by >agel :, ;inseisen C, van :ils 49, /eeters /9, Boutron7<uault 64, 4lavel7 4hapelon ., <omieu -, Tj_nneland A, ?lsen A, <oswall >, %itt /6, ?vervad =, <ohrmann S, =aaks <, #rogan #, Boeing 9, Trichopoulou A, Stratigakou 0, Nylis #, &ngeset #, ;und &, Skeie :, Berrino ., :rioni S, 6attiello A, 6asala :, Tumino <, Nanetti <, <os 66, Bueno7de76esBuita 9B, Ardana5 &, STnche5 6C, 9uerta C6, Amiano /, <odrZgue5 ;, 6anjer C, %irf`lt &, ;enner /, 9allmans :, Spencer &A, =ey TC, Bingham S, =haw =T, <inaldi S, Slimani >, Boffetta /, :allo 0, >orat T, <iboli &.'/ub6ed( ' 2( Beta7carotene intake and risk of postmenopausal breast cancer by Cumaan A?, 9olmberg ;, Nack 6, 6okdad A9, ?hlander &6, %olk A, Byers T.'/ub6ed( ' )( #ietary carotenoids and risk of breast cancer in 4hinese women by 9uang C/, Nhang 6, 9olman 4#, 8ie 8.'/ub6ed( ' *( 4irculating carotenoids and risk of breast cancerJ pooled analysis of

eight prospective studies by &liassen A9, 9endrickson SC, Brinton ;A, Buring C&, 4ampos 9, #ai H, #organ C., .ranke AA, :ao ET, :oodman 6T, 9allmans :, 9el5lsouer =C, 9offman7Bolton C, 9ult[n =, Sesso 9#, Sowell A;, Tamimi <6, Toniolo /, %ilkens ;<, %inkvist A, Neleniuch7 CacBuotte A'/ub6ed( ' +(. 4arotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor statusJ a pooled analysis of " prospective cohort studies by Nhang 8, Spiegelman #, Baglietto ;, Bernstein ;, Boggs #A, van den Brandt /A, Buring C&, :apstur S6, :iles ::, :iovannucci &, :oodman :, 9ankinson S&, 9el5lsouer =C, 9orn7<oss /;, -noue 6, Cung S, =hudyakov /, ;arsson S4, ;of 6, 6c4ullough 6;, 6iller AB, >euhouser 6;, /almer C<, /ark E, <obien =, <ohan T&, <oss CA, Schouten ;C, Shikany C6, Tsugane S, 0isvanathan =, %eiderpass &, %olk A, %illett %4, Nhang S6, Niegler <:, Smith7%arner SA.'/ub6ed( ' ,( 4arotenoids and breast cancer riskJ a meta7analysis and meta7regression by 9u ., %ang Ei B, Nhang %, ;iang C, ;in 4, ;i #, %ang ., /ang #, Nhao E.'/ub6ed( ' 1( 4ombined effects of antio$idant vitamin and >?S) genetic polymorphisms on breast cancer risk in women by ;ee SA, ;ee =6, Eoo =E, >oh #E, Ahn S9, =ang #.'/ub6ed( ' "( Antio$idants and breast cancer risk7 a population7based case7control study in 4anada by /an SE, Nhou C, :ibbons ;, 6orrison 9, %en S%W 4anadian 4ancer <egistries &pidemiology <esearch :roup R44<&<:S. '/ub6ed(. ' 2( Antio$idant vitamins and cytokines are altered in breast cancer by Abranches 60, 6endes 64, /ena :d, 6aia E4, <ibeiro S6, .ranceschini Sdo 4, de /aula S?, de .reitas <>, /elu5io 64.'/ub6ed( '23( #ietary carotenoids and risk of hormone receptor7defined breast cancer in a prospective cohort of Swedish women by ;arsson S4, Bergkvist ;, %olk A.'/ub6ed( '2 ( 4irculating carotenoids, mammographic density, and subseBuent risk of breast cancer by Tamimi <6, 4oldit5 :A, 9ankinson S&.'/ub6ed( '22( /lasma carotenoids, retinol, and tocopherols and risk of breast cancer by Tamimi <6, 9ankinson S&, 4ampos 9, Spiegelman #, Nhang S, 4oldit5 :A, %illett %4, 9unter #C.'/ub6ed( '2)( #ietary carotenoids and the risk of invasive breast cancer by 6ignone ;-, :iovannucci &, >ewcomb /A, Titus7&rnstoff ;, Trentham7#iet5 A, 9ampton C6, %illett %4, &gan =6.'/ub6ed( '2*( #ietary compared with blood concentrations of carotenoids and breast cancer riskJ a systematic review and meta7analysis of prospective studies by

Aune #, 4han #S, 0ieira A<, >avarro <osenblatt #A, 0ieira <, :reenwood #4, >orat T.'/ub6ed( '2+( Selected antio$idants and risk of hormone receptor7defined invasive breast cancers among postmenopausal women in the %omenIs 9ealth -nitiative ?bservational Study by 4ui E, Shikany C6, ;iu S, Shagufta E, <ohan T&.'/ub6ed( '2,( 6:6T genotype modulates the associations between cigarette smoking, dietary antio$idants and breast cancer risk by Shen C, Terry 6B, :ammon 6#, :audet 66, Teitelbaum S;, &ng S6, Sagiv S=, >eugut A-, Santella <6.'/ub6ed( '21( Antiproliferative activity of 4yanophora parado$a pigments in melanoma, breast and lung cancer cells by Baudelet /9, :age5 A;, B[rard CB, Cuin 4, Bridiau >, =aas <, Thi[ry 0, 4adoret C/, /icot ;.'/ub6ed( '2"( /lasma carotenoids, tocopherols, retinol and breast cancer riskJ results from the Shanghai %omen 9ealth Study 'S%9S( by #orjgochoo T, :ao ET, 4how %9, Shu 8?, ;i 9, Eang :, 4ai H, <othman >, 4ai 9, .ranke AA, Nheng %, #ai H.'/ub6ed( B. Vitamin B Com$le5 B.0. Vitamin B% Vitamin B% also known as <iboflavin, is a water7soluble, yellow7orange organic compound found abundantly in milk, meat, eggs, nuts, enriched flour, green vegetables, etc. The vitamin is essential for normal cellular growth and function and best known for converting energy from protein, fat, and carbohydrates during metabolism and its antio$idant effects in o$idation7reduction reactions. &pidemiological studies, focusing in the benefits of vitamin B2 in reduced risk and treatment of breast cancer have produced inconclusive results. Serum levels of riboflavin '<.( was found significantly be decreased in over7e$pressed of <. carrier protein women with breast cancer. Administration of <.7targeted 6647conjugate 'mitomycin 4 '664(7 conjugated >7'27hydro$ypropyl( methacrylamide '9/6A( Rused as macromolecular carriers to enhance therapeutic efficacy and limit side effects of anti7cancer chemotherapeutic agentsS enabled an increase in 664 uptake and nuclear locali5ation in cell cyle to induce cytoto$ic activity in in both 64.71 and S=B<7) cells' (. -n a follow7up of 23,1+, women from the 6elbourne 4ollaborative 4ohort Study, including modification by age, hormone receptor status and alcohol consumption showed a insignificant evidence for an inverse association between breast cancer risk and riboflavin intake'2(. ?ther in breast cancer risk among Capanese women, found no

correlation of vitamin B2 intake and no overall association with breast cancer risk')(')a(. Mnfortunately, a +7year survival rate study for in &<7!/<7 breast cancers among =orean women, showed that a high intake of vitamin B2 and folate statistically elevated the 9< of breast cancer progression compared to a low intake'*(. -n postmenopausal women with breast cancer, Tamo$ifen 'TA6( co administration with 4oen5yme H' 3(, <iboflavin and >iacin '4o<>( e$hibited a favorable impact on various blood chemistry profiles in reducing side effect of Tamo$ifen causes of o$idative stress with various biochemical derangements'+(, through increased the antio$idants status, while decreasing lipid and lipid pero$ides',('1(. -n an "* breast cancer patients randomi5ed to receive a daily supplement of 4oH' 3( 33 mg, riboflavin 3 mg and niacin +3 mg '4o<>(, one dosage per day along with tamo$ifen 'TA6( 3 mg twice a day, supplementing 4o<> decreased the levels of pro7angiogenic factors, increased the levels of anti7angiogenic factors and enhanced the efficacy of the treatment and might even offer protection from cancer metastases and recurrence'"('2(' 3(. &nergy7 modulating vitamins, riboflavin '*+ mg!kg body weight per d(, niacin ' 33 mg!kg body weight per d( and coen5yme H 3 '*3 mg!kg body weight per d( for 2" days in the e$periment against mammary carcinoma induced by the oral administration of 1, 27dimethylben5RaSanthracene '2+ mg!kg body weight(, showed an decreasing of the =rebs cycle and o$idative phosphorylation en5ymes and may be considered as a major therapeutic value in breast cancer' (. Taking altogether, vitamin B2 used conjunction with other energy vitamins and in co administration with Tami$ofen showed to enhance the efficacy of the chemo7agent by e$erting its antio$idant effects. -n fact, risk of breast cancer are associated to nutrient deficiency of vitamin B7 2, thiamin, folacin, iron, and riboflavin' 2(. ?ver doses for a prolong period may cause symptoms of skin rashes, hypersensitivity, high blood pressure etc., please make sure you follow the guideline of the -nstitute of 6edicine of the >ational Academies. Back to <esearched articles 7 /oints of view of 0itamins, .oods and 9erbs httpJ!!kylejnorton.blogspot.ca!p!blog7pagea2*.html Back to =yle C. >orton 9ome page httpJ!!kylejnorton.blogspot.ca

4eferences ' ( <iboflavin7targeted polymer conjugates for breast tumor delivery by Bareford ;6, Avaritt B<, :handehari 9, >an A, Swaan /%.'/ub6ed( '2( #ietary intake of B vitamins and methionine and breast cancer risk by Bassett C=, Baglietto ;, 9odge A6, Severi :, 9opper C;, &nglish #<, :iles ::.'/ub6ed( ')( #ietary intake of folate, vitamin B2, vitamin B,, vitamin B 2, genetic polymorphism of related en5ymes, and risk of breast cancerJ a case7control study in Capan by 6a &, -wasaki 6, =obayashi 6, =asuga E, Eokoyama S, ?numa 9, >ishimura 9, =usama <, Tsugane S.'/ub6ed( ')a( .olate, vitamin B 2 and postmenopausal breast cancer in a prospective study of .rench women by ;ajous 6, <omieu -, Sabia S, Boutron7<uault 64, 4lavel74hapelon ..'/ub6ed( '*( /rognosis of breast cancer is associated with one7carbon metabolism related nutrients among =orean women by ;ee E, ;ee SA, 4hoi CE, Song 6, Sung 9, Ceon S, /ark S=, Eoo =E, >oh #E, Ahn S9, =ang #. '/ub6ed( '+( &ffect of 4oen5yme H' 3(, <iboflavin and >iacin on Tamo$ifen treated postmenopausal breast cancer women with special reference to blood chemistry profiles by Euvaraj S, /remkumar 0:, Shanthi /, 0ijayasarathy =, :angadaran S:, Sachdanandam /.'/ub6ed( ',( Augmented antio$idant status in Tamo$ifen treated postmenopausal women with breast cancer on co7administration with 4oen5yme H 3, >iacin and <iboflavin by Euvaraj S, /remkumar 0:, 0ijayasarathy =, :angadaran S:, Sachdanandam /.'/ub6ed( '1( Augmented efficacy of tamo$ifen in rat breast tumorigenesis when gavaged along with riboflavin, niacin, and 4oH 3J effects on lipid pero$idation and antio$idants in mitochondria by /erumal SS, Shanthi /, Sachdanandam /.'/ub6ed( '"( Anti7angiogenic potential of 4oen5ymeH 3, riboflavin and niacin in breast cancer patients undergoing tamo$ifen therapy by /remkumar 0:, Euvaraj S, Sathish S, Shanthi /, Sachdanandam /.'/ub6ed( '2( Serum cytokine levels of interleukin7 beta, 7,, 7", tumour necrosis factor7alpha and vascular endothelial growth factor in breast cancer patients treated with tamo$ifen and supplemented with co7en5yme H' 3(, riboflavin and niacin by /remkumar 0:, Euvaraj S, 0ijayasarathy =, :angadaran S:, Sachdanandam /.'/ub6ed( ' 3( &ffect of coen5yme H 3, riboflavin and niacin on serum 4&A and 4A +7) levels in breast cancer patients undergoing tamo$ifen therapy by

/remkumar 0:, Euvaraj S, 0ijayasarathy =, :angadaran S:, Sachdanandam /.'/ub>6ed( ' ( &nergy7modulating vitamins77a new combinatorial therapy prevents cancer cache$ia in rat mammary carcinoma by /erumal SS, Shanthi /, Sachdanandam /.'/ub6ed( ' 2( Taste perception and breast cancerJ evidence of a role for diet by Ames 9:, :ee 6-, 9awrysh NC.'/ub6ed( B.%. Vitamin B' >iacin, is also known as vitamin B), nicotinic acid, an organic compound with the formula 4,9+>?2, found abundantly in chicken, beef, fish, cereal, peanuts and legumes. -t is best known for its effects in lowering cholesterol and triglycerides and removing to$ic from our body and promoting production of steroid hormones. &pidemiological studies, focused in niacin in reduced risk of breast cancer have produced conflict results. -n human breast cancer cell, combination of niacin and butyrate induced apoptosis, through activation of :/< 32A, a :7 protein7coupled receptor in inhibition of genes, involved in cell survival and anti7apoptotic signaling' (. But in the study of breast cancer risk among 4hinese women, niacin was found to be associated with &<@!/<@ breast cancer risk depending to the highest vs. lowest Buartile of intake in premenopausal women'2(. Mnfortunately, some researchers indicated that regardless to the doses, even 6ega7dose vitamins and minerals did not improve the breast cancer7specific survival and disease7free survival times in breast cancer patients'2a(. The study of potent antio$idant >iacin '4o<>(, co administration with Tamo$ifen 'TA6( showed favorable impact on various blood chemistry profiles and may be considered as a co7administrating antio$idants with conventional chemotherapy but large scale randomi5ed studies over a longer time span are reBuired to ascertain the safety and efficacy')(. -n tumour angiogenesis, the co administrations also decreased the levels of pro7angiogenic factors which reduced the tumor burden in protection from cancer metastases and recurrence'*(. ?ral administration of daily supplement of 33 mg co7en5yme H 3, 3 mg riboflavin and +3 mg niacin '4o<>(, one dosage per d along with 3 mg tamo$ifen twice per day in breast caner patients showed to reduce tumor burden by significant increase in poly'A#/7ribose polymerase levels'#ifferentiation, proliferation, and

tumor transformation and >ormal or abnormal recovery from #>A damage( and disappearance of <ASS. A'involved in early tumorigenesis( #>A methylation patterns'+(. -n postmenopausal women with breast cancer, the above combination significantly increased the A?'antio$idants( status, while decreasing lipid and lipid pero$ides'free radical(',(. >iacin is found effectively in reduced risk of breast cancer when co administrated. 4ombination with other vitamins and Tamo$ifen 'TA6( showed to provide protection and management in the process of breast cancer treatments, through e$hibition of antio$idants status and decreased free radical e$pression. /lease make sure to follow the guideline of the -nstitute of 6edicine of the >ational Academies. ?verdoses of vitamin B) may induce symptoms of severe skin flushing combined with di55iness, rapid heartbeat, itching, nausea, vomiting, abdominal pain, etc. 4eferences ' ( The niacin!butyrate receptor :/< 32A suppresses mammary tumorigenesis by inhibiting cell survival by &langovan S, /athania <, <amachandran S, Ananth S, /adia <>, ;an ;, Singh >, 6artin /6, 9awthorn ;, /rasad /#, :anapathy 0, Thangaraju 6.'/ub6ed( '2( #ietary B vitamin and methionine intakes and breast cancer risk among 4hinese women by Shrubsole 6C, Shu 8?, ;i 9;, 4ai 9, Eang :, :ao ET, :ao C, Nheng %.'/ub6ed( '2a( 6ega7dose vitamins and minerals in the treatment of non7metastatic breast cancerJ an historical cohort study by ;esperance 6;, ?livotto -A, .orde >, Nhao E, Speers 4, .oster 9, Tsao 6, 6ac/herson >, 9offer A. '/ub6ed( ')( &ffect of 4oen5yme H' 3(, <iboflavin and >iacin on Tamo$ifen treated postmenopausal breast cancer women with special reference to blood chemistry profiles by Euvaraj S, /remkumar 0:, Shanthi /, 0ijayasarathy =, :angadaran S:, Sachdanandam /.'/ub6ed( '*( Anti7angiogenic potential of 4oen5ymeH 3, riboflavin and niacin in breast cancer patients undergoing tamo$ifen therapy by /remkumar 0:, Euvaraj S, Sathish S, Shanthi /, Sachdanandam /.'/ub6ed( '+( 4o7en5yme H 3, riboflavin and niacin supplementation on alteration of #>A repair en5yme and #>A methylation in breast cancer patients undergoing tamo$ifen therapy by /remkumar 0:, Euvaraj S, Shanthi /, Sachdanandam /.'/ub6ed( ',( Augmented antio$idant status in Tamo$ifen treated postmenopausal

women with breast cancer on co7administration with 4oen5yme H 3, >iacin and <iboflavin by Euvaraj S, /remkumar 0:, 0ijayasarathy =, :angadaran S:, Sachdanandam /.'/ub6ed( B.'. Vitamin B* &pidemiological studies focusing vitamin B, in reduced risk of breast cancer have produced conflict results. But the widespread of breast cancer has caused many concerns in the world leaders and scientific community. &very year, over 2+3,333 new cases of breast cancer were e$pected to be diagnosed in women in the M.S. alone and the risk of getting invasive breast cancer during life time of a women is !". 0itamin B+, also known as /antothenic acid or pantothenate is a water soluble vitamin found abundantly in avocado, banana, dried beans, meat, nuts and whole grains cereals etc., with functions of amino acid, glucose and lipid metabolism, neurotransmitter synthesishistamine synthesis, hemoglobin synthesis and function gene e$pression. -n postmenopausal women, vitamin B,'Serum pyrido$al +I7phosphate '/;/, active form of vitamin B,( levels( might be inversely associated with breast cancer risk' (' a(. But in a case7control study in Bra5ilian women, 6T9.< polymorphisms and dietary intake of vitamin B, had no overall association with breast cancer risk'2(. Study of the 4hinese women, genetic mutation of 6T9.< and vitamin B , were associated with risk of breast cancer')(. #ietary intake of one7carbon nutrients, particularly folate, vitamin B'2( 'riboflavin(, vitamin B',( , vitamin B' 2( , and choline also linked to the risk of cancers of the colon and breast in both human and animal studies and maternal intake of these nutrients during gestation may also have an impact on the risk of cancer in offspring later in life')a(. -n Capanese women study, neither dietary intake of folate, vitamin B2, vitamin B,, or vitamin B 2 nor polymorphisms of 6T9.< or 6T< genes were significantly associated with breast cancer risk'*(. -n estrogen receptor '&<( and progesterone receptor '/<( breast cancers, dietary vitamin B, intakes were inversely associated with breast cancer risk, regardless to &< and!or /< status'+(. -n postmenopausal breast cancer study, women with highest Buartile range of plasma /;/ concentrations are associated to )3A reduced risk of invasive breast cancer compared with the women in the lowest /;/ Buartile',('1('"(. -n rodent models, high dose of B',( also suppressed cell proliferation and induced apoptosis of human breast adenocarcinoma 64.71 cells through induction of -:.B/7) by /> then by a p+)7specific inhibitor'"(

Taking all together, The effective of vitamin B,, in reduced risk of breast cancer is deemed controversial. But no doubt, certain vitamins and minerals deficiencies may play a critic role in the influence of development of breast cancer. ?ver doses may induced the symptoms of difficulty coordinating movement, numbness, sensory changes, etc., please make sure you follow the guideline of the -nstitute of 6edicine of the >ational Academies. 4eferences ' ( #ietary intake of folate, vitamin B,, and vitamin B 2, genetic polymorphism of related en5ymes, and risk of breast cancerJ a case7control study in Bra5ilian women by 6a &, -wasaki 6, Cunko -, 9amada :S, >ishimoto ->, 4arvalho S6, 6otola C Cr, ;aginha .6, Tsugane S. '/ub6ed( ' a( #ietary folate, vitamin B,, vitamin B 2 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status by Nhang 48, 9o S4, 4hen E6, ;in .E, .u C9, 4heng SN.'/ub6ed( '2( Association of dietary intake of folate, vitamin B, and B 2 and 6T9.< genotype with breast cancer risk by ;iu E, Nhou ;S, 8u 86, #eng ;H, 8iao H=.'/ub6ed( ')( #ietary intake of folate, vitamin B2, vitamin B,, vitamin B 2, genetic polymorphism of related en5ymes, and risk of breast cancerJ a case7control study in Capan by 6a &, -wasaki 6, =obayashi 6, =asuga E, Eokoyama S, ?numa 9, >ishimura 9, =usama <, Tsugane S.'/ub6ed( ')a( 6aternal one7carbon nutrient intake and cancer risk in offspring by 4iappio &#, 6ason CB, 4rott C%.'/ub6ed( '*( #ietary folate, vitamin B,, vitamin B 2 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status by Nhang 48, 9o S4, 4hen E6, ;in .E, .u C9, 4heng SN'/ub6ed( '+( /rediagnostic plasma pyrido$al +I7phosphate 'vitamin b,( levels and invasive breast carcinoma riskJ the multiethnic cohort by ;urie :, %ilkens ;<, Shvetsov EB, ?llberding >C, .ranke AA, 9enderson B&, =olonel ;>, :oodman 6T.'/ub6ed( ',( /lasma folate, vitamin B7,, vitamin B7 2, and risk of breast cancer in women by ;in C, ;ee -6, 4ook ><, Selhub C, 6anson C&, Buring C&, Nhang S6'/ub6ed( '1( Association of vitamin B,, vitamin B 2 and methionine with risk of breast cancerJ a dose7response meta7analysis by %u %, =ang S, Nhang #. '/ub6ed(

'"( 9igh dose of pyrido$ine induces -:.B/7) m<>A e$pression in 64.71 cells and its induction is inhibited by the p+)7specific inhibitor pifithrin7F by >akari 6, =anouchi 9, ?ka T.'/ub6ed( B.(. Folate .olate, also known as folic acid, vitamin B2, is a water soluble vitamin, found abundantly in leafy vegetables, citrus fruits, beans, whole grain, etc. The vitamin plays an important role in synthesi5e #>A, repair #>A, and methylate #>A as well as to act as a cofactor in certain biological reactions, production of red blood cells for anemia prevention. Scientific studies, linking folate in reduced risk of breast cancer have produced inconsistent results. -t may be due to race, menopausal status or &< status' (. -n comparison of the dietary intakes of folate, B7vitamins 'B2, B,, B 2( and methionine, showed that high intake of folate is marginally associated with a reduced lower risk for &<7 breast cancer' a(, among 9ispanic and non7 9ispanic white women'2(, but among Bra5ilian women, dietary intake of folate, had no overall association with breast cancer risk and high folate intake increased risk of breast cancer in premenopausal women with the 6T< 21+,:: genotype'women carry this gene have a subtly reduced risk of breast cancer')(('*(. -n breast cancer risk defined by oestrogen receptor '&<( and progesterone receptor '/<( status, dietary folate intake showed an significant inverse association of breast cancer risk in all subtypes of &< and /< status'+(. -n Capanese women with genotypes of 6T9.< or 6T<, dietary intake of folate and related B vitamins have no overall association with breast cancer risk in Capanese women',(. Mnfortunately. in rat model study, folate supplementation was found to be associated with significantly higher weight and volume of all mammary tumors and might enhance the progression of established mammary tumors'1(. Also in the study of at weaning, female pups, maternal folic acid supplementation significantly accelerated the rate of mammary adenocarcinoma appearance and significantly decreased #>A methyltransferase 'protect host #>A against degradation by restriction en5ymes( activity in nonneoplastic'not tumors( mammary glands of the offspring'"(. -n the finding of an anti breast caner conjugat used conjuction with #o$orubicin '#o$( which used for breast cancer treatment but causes serious side effects including cardioto$icity, conjugation of #o$7conjugated hairpin '#49( with folic acid '.A( is found to be effective in increased

internali5ation into breast cancer cells for safer and more effective chemotherapy with #o$'2(. -n 64.71 and 6#A76B72) breast cancer cells, hydrogel, based on ellagic acid and glycine containing folate acid significantly inhibit cell viability' 3(. -n nude mice carrying $enograft 64.71 tumours, folate inT68'Tamo$ifen(7loaded folate7targeted systems anticancer action of T68' (. ;ipotropes are methyl group7containing essential nutrients 'methionine, choline, folate and vitamin B 2( in the e$periment in 64.71 cells, showed to significantly reduced cell growth and increased apoptosis, through upregulation of caspase7)'mechanisms of apoptosis( and /+)'tumor antigen( en5yme activities' 2(. Also in the evaluation of 6T9.< 4,11T7A 22"4 polymorphisms in patients with breast cancer, showed that at dose of 23 nmol!; .A could enhance apoptosis in cases with women who carry 6T9.< 4,11T7A 22"4 genotype' )(. Taking altogether, folate used conjunction with other chem7drugs have shown effectively in enhancing the function the medicine in prevention and treatment of breast cancer cell lines with reduced side effects. ?verdoses of folate may cause stomach problems, sleep problems, skin reactions, sei5ures, etc., please make sure you follow the guideline of the -nstitute of 6edicine of the >ational Academies. 4eferences ' ( Associations of dietary folate, 0itamins B, and B 2 and methionine intake with risk of breast cancer among African American and &uropean American women by :ong N, Ambrosone 4B, 6c4ann S&, Nirpoli :, 4handran M, 9ong 44, Bovbjerg #9, Candorf ;, 4iupak :, /awlish =, ;u H, 9wang 9, =houry T, %iam B, Bandera &0.'/ub6ed( ' a( #ietary intake of folate, B7vitamins and methionine and breast cancer risk among 9ispanic and non79ispanic white women by Eang #, Baumgartner <>, Slattery 6;, %ang 4, :iuliano A<, 6urtaugh 6A, <isendal B4, Byers T, Baumgartner =B.'/ub6ed( '2( #ietary folate, vitamin B,, vitamin B 2 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status by Nhang 48, 9o S4, 4hen E6, ;in .E, .u C9, 4heng SN.'/ub6ed( ')( 4ancerJ >ew -nsights for the 9ealthcare /rofessionalJ 23 2 &dition '*( #ietary intake of folate, vitamin B,, and vitamin B 2, genetic polymorphism of related en5ymes, and risk of breast cancerJ a case7control

study in Bra5ilian women by 6a &, -wasaki 6, Cunko -, 9amada :S, >ishimoto ->, 4arvalho S6, 6otola C Cr, ;aginha .6, Tsugane S. '/ub6ed( '+( #ietary folate, vitamin B,, vitamin B 2 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status by Nhang 48, 9o S4, 4hen E6, ;in .E, .u C9, 4heng SN.'/ub6ed( ',( #ietary intake of folate, vitamin B2, vitamin B,, vitamin B 2, genetic polymorphism of related en5ymes, and risk of breast cancerJ a case7control study in Capan by 6a &, -wasaki 6, =obayashi 6, =asuga E, Eokoyama S, ?numa 9, >ishimura 9, =usama <, Tsugane S.'/ub6ed( '1( .olic Acid supplementation promotes mammary tumor progression in a rat model. by #eghan 6anshadi S , -shiguro ; , Sohn =C2, 6edline A), <enlund <*, 4ro$ford <+, =im E '/ub6ed( '"( &ffect of maternal and postweaning folic acid supplementation on mammary tumor risk in the offspring by ;y A, ;ee 9, 4hen C, Sie ==, <enlund <, 6edline A, Sohn =C, 4ro$ford <, Thompson ;M, =im E-. '/ub6ed( '2(Site7Specific #>A7#o$orubicin 4onjugates #isplay &nhanced 4ytoto$icity to Breast 4ancer 4ells by Stuart 49, 9orita #A, Thomas 6C, Salsbury .< Cr, ;ively 6?, :meiner %9.'/ub6ed( ' 3( Anticancer activity of a hydrogel containing folic acid towards 64.71 and 6#A76B72) cells by Trombino S, .errarelli T, /ellegrino 6, <icchio &, 6auro ;, AndV S, /icci >, 4assano <.'/ub6ed( ' ( Targeting Tamo$ifen to Breast 4ancer 8enograft TumoursJ /reclinical &fficacy of .olate7Attached >anoparticles Based on Alginate7 4ysteine!#isulphide7Bond7<educed Albumin by 6artZne5 A, 6ubi5 &, TeijUn 4, -glesias -, TeijUn C6, Blanco 6#.'/ub6ed( ' 2( ;ipotropes enhance the anti7proliferative effect of chemotherapeutic drugs in 64.71 human breast cancer cells by 4ho =, 6abasa ;, %alters 6%, /ark 4S.'/ub6ed( ' )( -nteractions between 6T9.< 4,11T7A 22"4 variants and folic acid deficiency affect breast cancer risk in a 4hinese population by %u 8E, >i C, 8u %C, Nhou T, %ang 8.'/ub6ed( B.*. Vitamin B0% Vitamin B0%, also known as cobalamin, a water7soluble vitamin, found abundantly in a variety of foods, such as fish, shellfish, meat, eggs, dairy products, etc. plays an important role in regulating the functions of nervous system and formation of blood.

&pidemiological studies linking levels of plasma of vitamin B 2 in reduced risk of breast cancer have produced inconclusive results. -n premenopausal women, /lasma vitamin B' 2( levels were inversely associated with breast cancer risk' (' a(' b(' c(. Mnfortunately, in the study of the same, showed vitamin B7 2, may confer little or no reduction in overall risk of developing breast cancer '2(')(')a(. -n human breast cancer cell line, 64.71 and normal mammary cells, 64.7 3A, lipotropes containing methionine, choline, folate, and vitamin B 2, showed an decrease of e$pression of bcl72 in regulating apoptosis in lipotrope7treated 64.71 cells of these suggestion of blocking Bcl72 might prove useful in sensiti5ing tumor cells to chemotherapy7induced apoptosis'*(. -n rat fed with ;ipotropes showed a reduction of tumor multiplicity and tumor volume significantly through decreased e$pression of histone deacetylase '9dac ( and #>A methyltransferase '#nmt ( genes in tumor tissues of the rats'+(. -n the study of 6aternal high7methyl diet, ;ipotropes showed significantly decreased tumor incidence, tumor multiplicity and tumor volume, while also displaying a significant increase in survival rate and tumor latency in rat offspring',( and enhanced the efficacy of chemo durgs, SA9A and #?8 through induced apoptosis, inhibited cell growth, and displayed anti7proliferation'1(. Taking all together, one can say that the effective of vitamin B 2 in reduced risk of breast cancer and enhanced the efficacy of chemo7drugs was found in conjunction with other members of the methyl group but not the vitamin itself. ?ver doses of the vitamin may induce symptoms of to$icity, including headache, giddiness and abnormal heart functioning, etc., please make sure to follow the guideline of the -nstitute of 6edicine of the >ational Academies. 4eferences ' ( /lasma folate, vitamin B,, vitamin B 2, homocysteine, and risk of breast cancer by Nhang S6, %illett %4, Selhub C, 9unter #C, :iovannucci &;, 9olmes 6#, 4oldit5 :A, 9ankinson S&.'/ub6ed( ' a( Association of dietary intake of folate, vitamin B, and B 2 and 6T9.< genotype with breast cancer risk by ;iu E, Nhou ;S, 8u 86, #eng ;H, 8iao H=.'/ub6ed( ' b( #ietary intake of folate, B7vitamins and methionine and breast cancer risk among 9ispanic and non79ispanic white women by Eang #, Baumgartner <>, Slattery 6;, %ang 4, :iuliano A<, 6urtaugh 6A,

<isendal B4, Byers T, Baumgartner =B.'/ub6ed( ' c( .olate, vitamin B 2 and postmenopausal breast cancer in a prospective study of .rench women by ;ajous 6, <omieu -, Sabia S, Boutron7<uault 64, 4lavel74hapelon ..'/ub6ed( '2( /lasma folate, vitamin B7,, vitamin B7 2, and risk of breast cancer in women by ;in C, ;ee -6, 4ook ><, Selhub C, 6anson C&, Buring C&, Nhang S6.'/ub6ed( ')( /lasma folate, vitamin B,, vitamin B 2, and homocysteine and pancreatic cancer risk in four large cohorts by Schernhammer &, %olpin B, <ifai >, 4ochrane B, 6anson CA, 6a C, :iovannucci &, Thomson 4, Stampfer 6C, .uchs 4.'/ub6ed( ')a( &ffect of combined folic acid, vitamin B,, and vitamin B 2 on cancer risk in womenJ a randomi5ed trial by Nhang S6, 4ook ><, Albert 46, :a5iano C6, Buring C&, 6anson C&.'/ub6ed( '*( ;ipotropes regulate B4;72 gene e$pression in the human breast cancer cell line, 64.71 by 9yung 9. =im, 4hung S. /ark'/ub6ed( '+( /ubertal supplementation of lipotropes in female rats reduces mammary cancer risk by suppressing histone deacetylase by 4ho =, 4hoi %S, 4rane 4;, /ark 4S.'/ub6ed( ',( 6aternal high7methyl diet suppresses mammary carcinogenesis in female rat offspring by 4ho =, 6abasa ;, Bae S, %alters 6%, /ark 4S. '/ub6ed( '1( ;ipotropes enhance the anti7proliferative effect of chemotherapeutic drugs in 64.71 human breast cancer cells by 4ho =, 6abasa ;, %alters 6%, /ark 4S.'/ub6ed( C. Vitamin C 0itamin 4, also known as ;7ascorbic acid, is a water7soluble vitamin, found in fresh fruits, berries and green vegetables. -t is best known for its free radical scavengers activity and regenerating o$idi5ed !itamin & for immune support. &pidemiological studies linking vitamin 4 in reduced risk of breast cancer may be inconclusive' (' a(' b(, but no doubt in acceptance of improved Buality of life'2(. 6acro nutrients intake may form an important parts in breast cancer patients in providing vital support for treatment.')(. There was a report of intake of supplementation of multiple vitamin, beta7carotene, vitamin 4, vitamin & and 5inc in postmenopausal women for 3 or more years may protect women from developing breast cancer')a(. %omen with breast cancer in the -ndian population, were found to have a

lower levels of mean vitamin 4, vitamin & and selenium than controls. if the levels of mean vitamin 4, vitamin & and selenium increased by unit, the risk of breast cancer was reduced by 1A')b(. -n breast cancer survival, dietary vitamin 4 intake before breast cancer diagnosis may be associated with breast cancer survival. but not in post7 diagnosis'*(. 9igh intake of ascorbic acid was in associated to reduce risk of breast cancer incidence in overweight women and women with high consumption of linoleic acid 'average consumption of more than , grams of linoleic acid per day('+( and insignificant risk in other breast cancer patients',(. ?n inflammation in cancer patients, high dose intravenous ascorbic acid therapy, decreased the levels of 47reactive protein thus reduced inflammation correlated with decreases in tumor marker levels'1(. 0itamin 4 supplements and Anthocyanin '-$orc( at a dose of 2 tablets!day, starting from 3 days before the radiation treatment until 3 days after the end of treatment was found to be protective against skin damage to patient undergoing adjuvant chemotherapy'"(. -n estrogen7induced breast carcinogenesis, vitamin 4 '0it 4( and butylated hydro$yanisole 'B9A( found to be effective in inhibition of 1D7estradiol '&2(7mediated o$idative stress and o$idative #>A damage by preventing the decreasing ><.2'antio$idant response pathway( and ?:: 'base e$cision repair.( levels'2(. -n the study of the same but in 64.7 3A cells, the combination also decreased &27mediated increase in "7?9d:'6arker detected in cancer patients( levels in the mammary tissues, induced S?#) '&$tracellular supero$ide dismutase R4u7NnS( through ><.2 /athway to defense against o$idative stress and in the prevention of estrogen7 mediated breast cancer' 3(. An increased e$pression of the mi<72)'<egulate &$pression of Tumor Suppressor :ene( was found in 1D7estradiol '&2(7treated mammary tissues and in human breast cell lines, treatment with vitamin 4 reverted &27 mediated increase in mi<72) levels by upregulating e$pression ><.2 antio$idant response pathway' (. -n *T breast cancer cells in vitamin 47 deficient mice, Ascorbic acid delayed the progress of metastasis, tumor growth and inflammatory cytokine secretion 'decreased serum inflammatory cytokine interleukin '-;(7,( as well as enhanced encapsulation of tumors' 2(. -n ;7ascorbate ';7ascorbic acid, vitamin 4(, increasing the concentration e$hibited the autophagic damage to functional S04T7 2'antibody( sensiti5es breast cancer cells' )(. -n B ,. 3, ;7ascorbate also caused induction of a proo$idant state, subseBuent reduction in mitochondrial membrane potential to induced apoptosis in a caspase7"'4ell apoptosis(7independent manner' *(. -n the usage of glucan, resveratrol and

vitamin 4, the combination showed the strongest activator of phagocytosis 'immune cell activation( and antibody formation to suppress the growth of breast and lung tumors, through stimulation of apoptosis' +(. -n *T cancer cell line, combined with ascorbate, 6n'---(>7alkylpyridylporphyrins '6n/s( inhibited cancer cells via pero$ide produced outside of the cell through enhancing tumour o$idative stress and tumor growth suppression' ,(. -n Ata$ia telangiectasia mutated 'AT6( diplotype on the breast cancer, vitamin 4 enhanced the increase of AT6 to reduce the risk of breast cancer.' 1(. -n &'2( metabolism and o$idant stress in involved in estrogen7induced breast cancer development, vitamin 4 reducesd the incidence of estrogen7induced mammary tumors, increased tumor latency and decreases o$idative stress in vivo' "(. -n S=7B<) and 9s+1"T breast cancer cell lines, 0itamin 4 treatment induced A-.'apoptosis7inducing factor( mediation of cell death pathway of the breast cancer cell lines independent to caspase pathway' 2(. -n human breast cancer cell line 64.71, combination of <etinoic acid and ascorbic acid inhibited the proliferation of human breast cancer cells through altering their gene e$pression related to antio$idation processes and the proliferation inhibitory pathway'23(. Taking altogether, without going into reviews, vitamin 4 is found to be effective in reduced risk and a potent agent for treatment of breast cancer. #aily ingestion of high7dose vitamin 4 may be considered safe, but in rare incidence, overdoses in a prolonged period of time, may cause intra7renal o$alate crystal deposition, a fatal nephroto$icity'2 ('22(. 4eferences ' ( 0itamin 4 suppresses cell death in 64.71 human breast cancer cells induced by tamo$ifen by Subramani T, Eeap S=, 9o %E, 9o 4;, ?mar A<, A5i5 SA, <ahman >6, Alitheen >B.'/ub6ed( ' a( 0itamin supplement consumption and breast cancer riskJ a review by 6isotti A6, :nagnarella /.'/ub6ed( ' b( #ietary fiber, vitamins A, 4, and &, and risk of breast cancerJ a cohort study by <ohan T&, 9owe :<, .riedenreich 46, Cain 6, 6iller AB. '/ub6ed( '2( -ntravenous vitamin 4 administration improves Buality of life in breast cancer patients during chemo7!radiotherapy and aftercareJ results of a retrospective, multicentre, epidemiological cohort study in :ermany by 0ollbracht 4, Schneider B, ;eendert 0, %eiss :, Auerbach ;, Beuth C.

'/ub6ed( ')( >utritional assessment of selected patients with cancer. Surwillo A, %awr5yniak A.'/ub6ed( ')a( Antio$idants and breast cancer risk7 a population7based case7control study in 4anada by /an SE, Nhou C, :ibbons ;, 6orrison 9, %en S%W 4anadian 4ancer <egistries &pidemiology <esearch :roup R44<&<:S. '/ub6ed( ')b( Association between breast cancer and vitamin 4, vitamin & and selenium levelsJ results of a case7control study in -ndia by Singh /, =apil M, Shukla >=, #eo S, #wivedi S>.'/ub6ed( '*( 0itamin 4 intake and breast cancer mortality in a cohort of Swedish women by 9arris 9<, Bergkvist ;, %olk A.'/ub6ed( '+( #ietary antio$idant vitamins, retinol, and breast cancer incidence in a cohort of Swedish women by 6ichels =B, 9olmberg ;, Bergkvist ;, ;jung 9, Bruce A, %olk A.'/ub6ed( ',( 0itamins 4 and &, retinol, beta7carotene and dietary fibre in relation to breast cancer riskJ a prospective cohort study. by 0erhoeven #T, Assen >, :oldbohm <A, #orant &, van It 0eer /, Sturmans ., 9ermus <C, van den Brandt /A.'/ub6ed(. '1( &ffect of high7dose intravenous vitamin 4 on inflammation in cancer patients by 6ikirova >, 4asciari C, <ogers A, Taylor /.'/ub6ed( '"( Skin to$icity from e$ternal beam radiation therapy in breast cancer patientsJ protective effects of <esveratrol, ;ycopene, 0itamin 4 and anthocianin '-$orc( by #i .ranco <, 4alvanese 6, 6urino /, 6an5o <, :uida 4, #i :ennaro #, Anania 4, <avo 0.'/ub6ed( '2( Antio$idant7mediated up7regulation of ?:: via ><.2 induction is associated with inhibition of o$idative #>A damage in estrogen7induced breast cancer by Singh B, 4hatterjee A, <onghe A6, Bhat >=, Bhat 9='/ub6ed(. ' 3( Supero$ide dismutase ) is induced by antio$idants, inhibits o$idative #>A damage and is associated with inhibition of estrogen7induced breast cancer by Singh B, Bhat 9=.'/ub6ed( ' ( 6icro<>A72) regulates ><.2 e$pression and is associated with breast carcinogenesis by Singh B, <onghe A6, 4hatterjee A, Bhat >=, Bhat 9=. '/ub6ed( ' 2( Ascorbate supplementation inhibits growth and metastasis of B ,.? melanoma and *T breast cancer cells in vitamin 47deficient mice by 4ha C, <oomi 6%, -vanov 0, =alinovsky T, >ied5wiecki A, <ath 6.'/ub6ed( ' )( S04T72 in breast cancer acts as an indicator for ;7ascorbate treatment by 9ong S%, ;ee S9, 6oon C9, 9wang CC, =im #&, =o &, =im 9S, 4ho

-C, =ang CS, =im #C, =im C&, Shin CS, Cung #C, Ceong EC, 4ho BC, =im T%, ;ee CS, =ang CS, 9wang E-, >oh #E, Cin #9, ;ee %C.'/ub6ed( ' *( ;7ascorbic acid 'vitamin 4( induces the apoptosis of B , murine melanoma cells via a caspase7"7independent pathway by =ang CS, 4ho #, =im E-, 9ahm &, Eang E, =im #, 9ur #, /ark 9, Bang S, 9wang E-, ;ee %C.'/ub6ed( ' +( 4ombination of glucan, resveratrol and vitamin 4 demonstrates strong anti7tumor potential. 0etvicka 0, 0etvickova C.'/ub6ed( ' ,( 4ytoto$ic effects of 6n'---( >7alkylpyridylporphyrins in the presence of cellular reductant, ascorbate by Ee 8, .els #, Tovmasyan A, Aird =6, #edeugd 4, Allensworth C;, =os -, /ark %, Spasojevic -, #evi :<, #ewhirst 6%, ;eong =%, Batinic79aberle -.'/ub6ed( ' 1( Antio$idant vitamins intake, ata$ia telangiectasia mutated 'AT6( genetic polymorphisms, and breast cancer risk by ;ee SA, ;ee =6, ;ee SC, Eoo =E, /ark S=, >oh #E, Ahn S9, =ang #.'/ub6ed( ' "( 0itamin 4 and alpha7naphthoflavone prevent estrogen7induced mammary tumors and decrease o$idative stress in female A4- rats by 6ense S6, Singh B, <emotti ., ;iu 8, Bhat 9=.'/ub6ed( ' 2( Ascorbate 'vitamin 4( induces cell death through the apoptosis7 inducing factor in human breast cancer cells by 9ong S%, Cin #9, 9ahm &S, Eim S9, ;im CS, =im =-, Eang E, ;ee SS, =ang CS, ;ee %C, ;ee %=, ;ee 6S.'/ub6ed( '23( <etinoic acid and ascorbic acid act synergistically in inhibiting human breast cancer cell proliferation by =im =>, /ie C&, /ark C9, /ark E9, =im 9%, =im 6=.'/ub6ed( '2 ( .atal vitamin 47associated acute renal failure by 6c9ugh :C, :raber 6;, .reebairn <4.'/ub6ed( '22( Ascorbic acid overdosingJ a risk factor for calcium o$alate nephrolithiasis by Mrivet5ky 6, =essaris #, Smith A#.'/ub6ed( <. Vitamin < Vitamin < is a fat7soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and 5inc. &pidemiological studies, linking vitamin # in reduced risk of breast caner focused in levels and plasma levels of vitamin # are still on debates. -t may be due to age of subjects, menstrual stage, race, etc.. But the prevalence and

wide spread of breast cancer have caused some concerns in the governments and researched community. &very year, over 2+3,333 new cases of breast cancer were e$pected to be diagnosed in women in the M.S. alone and the risk of getting invasive breast cancer during life time of a women is !". 6e!els of free circ lation of !itamin < are correlated with ris/ of Breast cancer Suggestions of levels of plasma 2+7hydro$yvitamin # '2+'?9(#( in a breast cancer risk differentiation by menopause, showed an inverse association beyond a threshold of 21 ng!m;, but with flattening of effects above )+ ng!m;' (and low levels of 2+'?9(# are at higher risk of breast cancer' (. -n 4hinese breast cancer patients low vitamin # status was found to be associated to increased risk of breast cancer'2(. -n breast cancer risk in an Australian population, in differentiation of plasma vitamin # levels indicated that 2+'?9(# concentration below 1+ nmol!; was associated with a significantly higher risk of breast cancer')(. -n progesterone receptor negative breast cancer, restricted to premenopausal women only, plasma 2+'?9(# concentrations. significant inverse association in breast cancer risk'*( -n post postmenopausal breast cancer risk, 4irculating 2+'?9(#) and 2+'?9(# were found to associated with a reduced risk among whites, but not in other ethnic groups'+(. -n :enetic factor study, some vitamin # receptor '0#<( gene polymorphisms, such as Bsm , poly'A(, TaB , Apa are associated to risk of breast cancer',(. 2,333 -M vitamin #7) intake inhibited breast cancer proliferation through reduced 4?82 e$pression'correlated with primary tumor si5e(',a(. Mnfortunately, some suggested that vitamin #, regardless to dosage do not significantly affect breast cancer risk, treatment efficacy depending to highest dosage of vitamin # and in combination with calcium',b(. &he benefits -n a few randomi5ed clinical trials '<T4( assessing whether either vitamin # intake or serum levels of 2+ hydro$yvitamin # '2+?9#( correlate 'inversely( with cancer development, suggested that the vitamin # intake or serum levels of 2+ hydro$yvitamin # '2+?9#( reduced risk of cancers by e$hibiting its anticancer effects, through the impact in a number of cellular mechanisms'1(. -n triple negative!basal7like breast cancer, ,2+7 dihydro$yvitamin #) ' ,2+#( suppressed multiple proteins that are reBuired for survival of triple7negative!basal7like breast cancer cells through 0#< in down regulated breast cancer invasion and metastasis and up regulated anti7 profilaerative and apoptic e$pression'"(. -n Two 0#<=? '=?2*3, =?2""(

and two %T '%T *+, %T21,( cell lines, ,2+7#ihydro$yvitamin #')( ' ,2+#')((, the active metabolite of vitamin #')(, inhibited the protein e$pression of 0#< through induced :'3(!:' ( arrest and apoptosis in knockout '0#<=?( and wild type '%T( mice'2(. -n &< negative, invasive human breast cancer cell line SM67 +2/T, ,2+'?9('2(#')( ' ,2+#')(( and &B 3"2, a novel vitamin # analogue, reduced SM67 +2/T cell growth subseBuent to elevation of p21'regulator of cell cycle progression at : and S phase( and p2 'cell cycle inhibitor( levels and inhibited SM67 +2/T cell invasion through an " micro6 6atrigel 'e$tract in measurement of the invasive activity of tumor cells(' 3(. -n human breast cancer cell line 64.7 1, 4alcitriol, calcipotriol '/<-7223 ( and tacalcitol '/<-72 2 (, the synthetic version of vitamin #, showed the antiproliferative activity. At higher doses of /<-72232 or /<-7223+, the analog e$pressed their anti breast cancer activity similar to Tamo$ifen through diminished mitochondrial membrane potential' in cell proliferation(, as well as the increased phosphatidylserine 'cell death( e$pression with increase in 0#< e$pression in /<-7223 , but not /<-72 2,' (. -n 64.71 breast cancer cells, 27nor72F7')7 hydro$ypropyl(7 F,2+7dihydro$yvitamin #) '6A<T7 3(, a vitamin # analog' 3337fold more active than F,2+'?9(2#)( suppressed 64.71 cells growth through cell cycle arrest and apoptotic induction through the upregulation of &7cadherin'tumor suppressors(, and the downregulation of Snail, Slug, and Twist, the transcription in regulate the e$pression of tumor suppressors such as &7cadherin' 2(. -n B<4A 7deficient'loss of the #>A repair protein +)B/ ( breast cancer cells, F,2+'?9(2#), an active form of vitamin #, stabili5ed +)B/ levels in tumor cells and restored the levels of +)B/ , resulting in increased genomic instability in response to /A</i or radiation, and reduced proliferation' )(. :c6A., the vitamin #7binding protein7derived macrophage activating factor e$hibited its anti breast cancers effects through stimulation of macrophages'a large white blood cell (in induction of apoptosis and eventually phagocyti5e them' *(. 9&<2, accounted for appro$imately 23A of human breast cancer cases, :emini vitamin # analog B8;3 2*, decreased activation of &rbB2 as well as other &rbB receptors, &rbB and &rbB), through repression of activated7 &rk !2'cell regulation(, activated7Akt'multiple cellular processes, including apoptosis(, c76yc'a regulator gene(, 4yc# 'regulating cell cycle progression(, and Bcl2'family of regulator proteins that regulate cell death( ' +(. -n &<@ B4a., vitamin # suppressed the &< e$pression and estrogen7 mediated signaling in B4a cells' ,(. -n 64.71 and 64.71!0#'<( breast cancer cells, insulin7like growth factor - '-:.7-( in , 2+7dihydro$yvitamin #) ' , 2+7#)(inhibited -:.7-!Akt pathways to cause apoptosis' 1(. -n

64. 3#4-S cells, :emini vitamin # B8;3 2* is found to decrease 4#** protein level'a transmembrane glycoprotein, is a major receptor for e$tracellular proteins involved in invasion and metastasis of human cancers(, suppressed STAT) 'development, progression, and maintenance of many human tumors(signaling, and inhibited invasion and proliferation' "( and inhibited the growth of &rbB2 overe$pressing mammary tumors through regulating the &rbB2!A=T!&<='proliferation( signaling pathways in &rbB27 positive mammary tumor growth' "(. -n 64.71 breast cancer cells, ;7 buthionine7S,<7sulfo$imine, a glutathione7depleting drug enhanced inhibition of ,2+'?9('2(#')( in all transformed breast cell lines through <?S mediation induced apoptosis' 2(. The disagreement of amount of vitamin # intake and plasma level in reduced risk and treatment of breast cancer may still need further studies, but the effective of vitamin # may not be denied. ?ver doses of vitamin # supplement may cause e$cessive calcium absorption, calcification, Mrinary stones etc. please make sure to follow the guideline of the -nstitute of 6edicine of the >ational Academies. 4eferences ' ( /lasma vitamin # levels, menopause, and risk of breast cancerJ dose7 response meta7analysis of prospective studies by Bauer S<, 9ankinson S&, Bertone7Cohnson &<, #ing &;.'/ubnmed( '2( 4orrelates of 2+79ydro$yvitamin # among 4hinese Breast 4ancer /atients by Shi ; , >echuta S2, :ao ET), Nheng E*, #orjgochoo T2, %u C2, 4ai H2, Nheng %2, ;u %*, Shu 8?2.'/ub6ed( ')( Association between 2+7hydro$yvitamin # concentration and breast cancer risk in an Australian populationJ an observational case7control study by Bilinski =, Boyages C.'/ub6ed( '*( /lasma 2+7hydro$yvitamin # and premenopausal breast cancer risk in a :erman case7control study by Abbas S, 4hang74laude C, ;inseisen C. '/ub6ed( '+( /lasma 2+7hydro$yvitamin #) is associated with decreased risk of postmenopausal breast cancer in whitesJ a nested case7control study in the multiethnic cohort study by =im E, .ranke AA, Shvetsov EB, %ilkens ;<, 4ooney <0, ;urie :, 6askarinec :, 9ernande5 BE, ;e 6archand ;, 9enderson B&, =olonel ;>, :oodman 6T.'/ub6ed( ',( 0itamin # receptor gene polymorphisms in breast and renal cancerJ 4urrent state and future approaches '<eview( by =han 6- , Bielecka N. ,

>ajm 6N2, Bartnik &), 45arnecki CS*, 45arnecka A6 , S5c5ylik 4 '/ub6ed( ',a( 0itamin # favorably alters the cancer promoting prostaglandin cascade by Hin %, Smith 4, Censen 6, 9olick 6., Sauter &<.'/ub6ed( ',b( 0itamin d supplementation and breast cancer preventionJ a systematic review and meta7analysis of randomi5ed clinical trials by Sperati ., 0ici /, 6augeri7Saccd 6, Stranges S, Santesso >, 6ariani ;, :iordano A, Sergi #, /i55uti ;, #i ;auro ;, 6ontella 6, 4rispo A, 6ottolese 6, Barba 6. '/ub6ed( '1( 0itamin # and cancerJ the promise not yet fulfilled by Bikle ##'/ub6ed(. '"( 6odeling vitamin # actions in triple negative!basal7like breast cancer by ;aporta &, %elsh C.'/ub6ed( '2( 4haracteri5ation of mammary tumor cell lines from wild type and vitamin #) receptor knockout mice by Ninser :6, 6c&leney =, %elsh C. '/ub6ed( ' 3( &fficacy of 0itamin # compounds to modulate estrogen receptor negative breast cancer growth and invasion by .lanagan ;, /ackman =, Cuba B, ?I>eill S, Tenniswood 6, %elsh C.'/ub6ed(. ' ( Synthesis and Biological Activity of #iastereomeric and :eometric Analogs of 4alcipotriol, /<-72232 and /<-7223+, Against 9uman 9;7,3 ;eukemia and 64.71 Breast 4ancer 4ells. by 6ilc5arek 6, 4hodyYski 6, .ilip7/surska B, 6artowic5 A, =rupa 6, =rajewski =, =utner A, %ietr5yk C.'/ub6ed( ' 2( 6A<T7 3, a less calcemic vitamin # analog, is more potent than F,2+7dihydro$yvitamin #) in inhibiting the metastatic potential of 64.71 breast cancer cells in vitro by 4hiang =4, 4hen S4, Eeh 4>, /ang C9, Shen S4, 9su CT, ;iu EE, 4hen ;%, =uo S., Takano 6, =ittaka A, Sun 44, Cuang 99, 4hen T4.'/ub6ed( ' )( >ovel roles of F,2+'?9(2#) on #>A repair provide new strategies for breast cancer treatment by :on5alo S.'/ub6ed(. ' *( A novel role for a major component of the vitamin # a$isJ vitamin # binding protein7derived macrophage activating factor induces human breast cancer cell apoptosis through stimulation of macrophages by Thyer ;, %ard &, Smith <, .iore 6:, 6agherini S, Branca CC, 6orucci :, :ulisano 6, <uggiero 6, /acini S.'/ub6ed( ' +( ?ral administration of a gemini vitamin # analog, a synthetic triterpenoid and the combination prevents mammary tumorigenesis driven by &rbB2 overe$pression by So CE, %ahler C&, Eoon T, Smolarek A=, ;in E, Shih %C, 6aehr 9, Mskokovic 6, ;iby =T, Sporn 6B, Suh >.

'/ub6ed(. ' ,( Transrepression of the estrogen receptor promoter by calcitriol in human breast cancer cells via two negative vitamin # response elements by Swami S, =rishnan A0, /eng ;, ;undBvist C, .eldman #.'/ub6ed(. ' 1( <ole of insulin7like growth factor binding protein7) in , 2+7 dihydro$yvitamin7d ) 7induced breast cancer cell apoptosis by Brosseau 4, /irianov :, 4olston =%.'/ub6ed( ' "( Targeting 4#**7STAT) signaling by :emini vitamin # analog leads to inhibition of invasion in basal7like breast cancer by So CE, Smolarek A=, Salerno #6, 6aehr 9, Mskokovic 6, ;iu ., Suh >.'/ub6ed( ' 2( Buthionine sulfo$imine and ,2+7dihydro$yvitamin # induce apoptosis in breast cancer cells via induction of reactive o$ygen species by Bohl ;/, ;iaudat A4, /icotto :, 6archionatti A6, >arvae5 4C, %elsh C, <odrigue5 0A, Tolosa de Talamoni >:.'/ub6ed( 8. Vitamin 8 &pidemiological studies, linking vitamin & in reduced risk of breast cancer focused on variant F7tocopherol with inconsistent results. -n recent study, research in e7tocopherol, f7tocopherol, have shown a promising potential as the vaiants e$erted a greater ability in reducing inflammation, cell proliferation, and inhibiting the development of mammary hyperplasia and tumorigenesis' (' a(' b( 0itamin &, a fat soluble vitamin, consisting eight different variants 'alpha7, beta7, gamma7, and delta7tocopherol and alpha7, beta7, gamma7, and delta7 tocotrienol( with varying levels of biological activity'2(, found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of en5ymatic activity, free radical scavenger, etc.. A cohort study from the Breast 4ancer Serum Bank in 4olumbia, free of cancer sample blood donated to the bank did not found any evidence for protective effects of alpha7tocopherol in breast cancer')(. ?bservation of her72!neu indicated the correlation with 9er2!neu receptor and reduced TA/ e$pression found in breast cancer stage and nodal stage in paired normal and cancerous breast tissue samples, F7tocopheryl succinate 'F7T?S(, a synthetic derivative of F7tocopherol, enhanced the efficacy of do$orubicin resulting in a reduction in cell viability in breast cancers')a(. -n 64.71 breast cancer cell line, dl7alpha7tocopherol showed evidence of a general

inhibition of cell proliferation')b(. -n 9&<72!neu breast cancer cells and in comparison of the anticancer effect of alpha7, gamma7, and delta7 tocotrienols with alpha7tocopheryl succinate 'alpha7T?S(, the non>al$ha form of T) is more potent in inhibition of cancer activity than the synthetic 0&7derivative alpha7T?S, possibly through the mitochondrial pathway, and the e$pression of senescent7like growth arrest markers'which provides a possible marker for the process( as p+)tumor antigen(, p2 'regulator of cell cycle progression at : and S phase(, , and p ,'multiple tumor suppressor ( ')c(. #elta7tocotrienol, isolated from the tocotrienol7rich fraction of palm oil, showed a positive effective against metastatic breast cancers')d(. ?ther in the study of estrogen7responsive 64.1 cells and the estrogen7 nonresponsive 6#A76B7*)+ cells, <<<7alpha7, beta7, gamma7and delta7 tocotrienols and and <<<7delta7tocopherol induced 6#A76B7*)+ cells to undergo apoptosis, with the e$ception of <<<7delta7tocopherol, the tocopherols 'alpha, beta, and gamma( and the acetate derivative of <<<7 alpha7tocopherol '<<<7alpha7tocopheryl acetate(')e(. -n aggressive triple negative 6#A76B72) cells and oestrogen7dependent 64.71 cells, tocotrienol7rich fraction 'T<.( and a tocotrienol7enriched fraction 'T&.( isolated from palm oil showed a positive effect in induction of anti7proliferation and apoptosis through #>A repair protein and >.7XB, an apoptotic cell death signalling pathway'*(. -n 9&<72!neu7overe$pressing human S=B<) and murine TMB? breast cancer cells, vitamin & form f7 tocotrienol 'f7T)( possessed significantly high cytoto$ic and apoptotic activity in S=B<) cells than other facttions of vitamin &, through mitochondrial destabili5ation, energy failure, and unbalanced activity of stress!survival 6A/=s, namely p)" ''highly e$pressed in aggressive and invasive breast cancers( and &<= !2'cell regulation( pathways'+(. -n human 6#A7mB72) breast cancer cells, delta7tocotrienol e$erted its anti cancer effect trough suppression of site7specific <b phosphorylation and mediation of by the loss of cyclin # ',(. -n estrogen7nonresponsive 6#A76B7*)+ and estrogen7responsive 64.71 human breast cancer cells, vitamin & succinate '0&S( or dl7alpha7tocopherol 'refers to eight naturally occurring and synthetic tocopherols and tocotrienols and their acetate and succinate derivatives(, induced apoptosis involving up7regulation of T:.7beta receptor -- 'tumor suppressor gene( e$pression and T:.7beta7'cell prcess(, .as7 'associated with the induction of apoptosis( and C>=7 'cellular apoptosis( signaling pathways'1(. These results indicated that tocotrienols e$erted directly inhibitory effects on the growth of breast cancer cells irrespective of estrogen receptor status, not via an estrogen receptor7

mediated pathway'"(. Also in human '64.71 and 6#A76#72) ( mammary tumor cells lines, e7 tocotrienol induced apoptosis through induction of autophagy with evidences of the presence of relatively large increase in the accumulation of monodansylcadaverine '6#4(7labeled vacuoles, a marker of autophagosome formation'2(. -n neoplastic'gene modification( @SA'high malignance( mammary epithelial cells, treatment with * micro6 gamma7 tocotrienol, a dose that inhibited @SA cell growth by more than +3A compared with that of untreated control cells, decreased intracellular levels of activated /-)=!Akt 'anti7apoptosis and increased cell proliferation( pathway' 3(. ?n mouse '@SA( and human '64.71, and 6#A76B72) ( mammary cancer cell lines, 4ombined e7tocotrienol and SM 21* '6et inhibitor( treatment resulted in synergistic inhibition through reduction in Akt 'multiple cellular processes( STAT !+ 'activator of transcription ,+ ( and >.XB'a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis( activation and corresponding blockade in epithelial7to7mesenchymal transition' a process by which epithelial cells lose their cell polarity and cell7cell adhesion and start a the initiation of metastasis for cancer progression.(, as indicated by increased e$pression of &7cadherin, D7catenin, and cytokeratins "! " 'epithelial markers( and corresponding reduction in vimentin 'mesenchymal marker( and reduction in cancer cell motility' (. -n other study, treatment of gamma7tocopherol 'eT( and gamma7tocotrienol 'eT)( in human breast cancer cell lines, induced apoptosis via de novo ceramide synthesis'key molecules in cellular life and death decisions and the precursors to comple$ sphingolipids found in membranes( dependent activation of C>=!49?/''4!&B/ homologous protein(!#<+ pro7apoptotic signaling' 2( and in e7tocopherol 'eT( alone, the variant showed to suppress inflammatory markers, inhibited &2 7induced cell proliferation, and up regulated //A<e'regulation of cellular differentiation, development, and metabolism( and >rf2 'antio$idant response pathway(e$pression in mammary hyperplasia' )( or modulated &< stress signaling targeting AT.)'activating transcription factor ), involved in the comple$ process of cellular stress response( in breast cancer cells' *(. -n 9&<2!neu, vitamin & analog namely alpha7tocopherylo$yacetic acid, inhibited the proliferation of kills both 9&<2!neu positive and 9&<2!neu negative breast cancer cells with less to$ic than e$isting chemotherapeutic drugs when used in combination with 9&<2!neu antibody' +(. Taken the evidences of the effects of tocotrienols, dietary vitamin & or

vitamin & supplement may provide significant health benefits in the reduced risk and prevention and!or treatment of breast cancer when used either alone or in combination with other anticancer agents' ,(. 4eferences ' ( 4hemopreventive activity of vitamin & in breast cancerJ a focus on e7 and f7tocopherol by Smolarek A=, Suh >.'/ub6ed( ' a( 6echanisms mediating the antiproliferative and apoptotic effects of vitamin & in mammary cancer cells by Sylvester /%, Shah SC.'/ub6ed( ' b( #ietary administration of f7 and e7tocopherol inhibits tumorigenesis in the animal model of estrogen receptor7positive, but not 9&<72 breast cancer by Smolarek A=, So CE, Burgess B, =ong A>, <euhl =, ;in E, Shih %C, ;i :, ;ee 6C, 4hen E=, Eang 4S, Suh >.'/ub6ed( '2( Traber 6:. 0itamin &. -nJ Shils 6&, Shike 6, <oss A4, 4aballero B, 4ousins <, eds. 6odern >utrition in 9ealth and #isease. 3th ed. Baltimore, 6#J ;ippincott %illiams g %ilkins, 233,W)2,7* . ')( <elationships of serum carotenoids, retinol, alpha7tocopherol, and selenium with breast cancer riskJ results from a prospective study in 4olumbia, 6issouri 'Mnited States( by #organ C., Sowell A, Swanson 4A, /otischman >, 6iller <, Schussler >, Stephenson 9& Cr'/ub6ed( ')a( Alteration of F7tocopherol7associated protein 'TA/( e$pression in human breast epithelial cells during breast cancer development by Tam =%, 9o 4T, ;ee %C, Tu S9, 9uang 4S, 4hen 4S, ;ee 49, %u 49, 9o ES. '/ub6ed( ')b( dl7alpha7tocopherol induces apoptosis in erythroleukemia, prostate, and breast cancer cells by Sigounas :, Anagnostou A, Steiner 6.'/ub6ed( ')c( :amma7 and delta7tocotrienols e$ert a more potent anticancer effect than alpha7tocopheryl succinate on breast cancer cell lines irrespective of 9&<72!neu e$pression by /ierpaoli &, 0iola 0, /ilolli ., /iroddi 6, :alli ., /rovinciali 6.'/ub6ed( ')d( Synthesis of fluorescent analogues of the anticancer natural products *7 hydro$yphenylmethylene hydantoin and delta7tocotrienol by 6udit 6, Behery .A, %ali 0B, Sylvester /%, &l Sayed =A.'/ub6ed( ')e( -nduction of apoptosis in human breast cancer cells by tocopherols and tocotrienols by Eu %, Simmons76enchaca 6, :apor A, Sanders B:, =line =.'/ub6ed(. '*( Tocotrienols promote apoptosis in human breast cancer cells by inducing poly'A#/7ribose( polymerase cleavage and inhibiting nuclear factor kappa7 B activity by ;oganathan <, Selvaduray =<, >esaretnam =, <adhakrishnan A=.'/ub6ed(

'+( 6itochondrial7dependent anticancer activity of f7tocotrienol and its synthetic derivatives in 9&<72!neu overe$pressing breast adenocarcinoma cells by 0iola 0, 4iffolilli S, ;egnaioli S, /iroddi 6, Betti 6, 6a55ini ., /ierpaoli &, /rovinciali 6, :alli ..'/ub6ed( ',( :rowth inhibition of human 6#A7mB72) breast cancer cells by delta7 tocotrienol is associated with loss of cyclin # !4#=* e$pression and accompanying changes in the state of phosphorylation of the retinoblastoma tumor suppressor gene product by &langovan S, 9sieh T4, %u C6. '/ub6ed( '1( /ro7apoptotic mechanisms of action of a novel vitamin & analog 'alpha7 T&A( and a naturally occurring form of vitamin & 'delta7tocotrienol( in 6#A76B7*)+ human breast cancer cells by Shun 64, Eu %, :apor A, /arsons <, Atkinson C, Sanders B:, =line =.'/ub6ed( '"( Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status by >esaretnam =, Stephen <, #ils <, #arbre /. '/ub6ed( '2(e7Tocotrienol7induced autophagy in malignant mammary cancer cells by Tiwari <0, /arajuli /, Sylvester /%.'/ub6ed( ' 3( :amma7tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing Akt and nuclear factor kappaB activity by Shah SC, Sylvester /%.'/ub6ed( ' ( 4ombined e7tocotrienol and 6et inhibitor treatment suppresses mammary cancer cell proliferation, epithelial7to7mesenchymal transition and migration by Ayoub >6, Akl 6<, Sylvester /%.'/ub6ed( ' 2( -nvolvement of de novo ceramide synthesis in gamma7tocopherol and gamma7tocotrienol7induced apoptosis in human breast cancer cells by :opalan A, Eu %, Ciang H, Cang E, Sanders B:, =line =.' 2( ' )( #ietary tocopherols inhibit cell proliferation, regulate e$pression of &<F, //A<e, and >rf2, and decrease serum inflammatory markers during the development of mammary hyperplasia by Smolarek A=, So CE, Thomas /&, ;ee 9C, /aul S, #ombrowski A, %ang 48, Saw 4;, =hor T?, =ong A>, <euhl =, ;ee 6C, Eang 4S, Suh >.'/ub6ed( ' *( :amma7tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells by /atacsil #, Tran AT, 4ho ES, Suy S, Saen5 ., 6alyukova -, <essom 9, 4ollins S/, 4larke <, =umar #.'/ub6ed( ' +( The vitamin & analog, alpha7tocopherylo$yacetic acid enhances the anti7tumor activity of trastu5umab against 9&<2!neu7e$pressing breast cancer by 9ahn T, Bradley7#unlop #C, 9urley ;9, 0on79off #, :ately S, 6ary #;, ;u 9, /enichet 6;, Besselsen #:, 4ole BB, 6eeuwsen T,

%alker &, Akporiaye &T.'/ub6ed( ' ,( /otential role of tocotrienols in the treatment and prevention of breast cancer by Sylvester /%, Akl 6<, 6alaviya A, /arajuli /, Ananthula S, Tiwari <0, Ayoub >6.'/ub6ed( F. Vitamin K 0itamin ='= , phylloBuinoneW =2, menaBuinones(, is a fat soluble vitamin, found abundantly in leafy green vegetables, broccoli, and Brussels sprouts, etc. -t is best known for promotion of coagulation and bone health. &pidemiological studies focused in the synthetic version of vitamin ='0k)( in reduced risk and treatment of breast cancer have proven successful in certain e$tents. -n comparison of the anti cancer effects of 0itamin = '0=( congeners, vitamin =)'6enadione (, a synthetic analogue with the same properties as provitaminis was found to be most potent in treating various types of cancer, including breast cancer' ( -n comparison the inhibition effects of vitamin =, =) and warfarin in human cancer cell lines, the combination of ) 4ompletely inhibited of ; 2 3 growth in flask culture at concentrations of 233 micrograms!ml of warfarin, 1+ micrograms!ml of vitamin = , and * micrograms!ml of vitamin =). The combination =) and warfarin enhanced cytoto$icity at doses depending manner. 0itamin =) alone was also cytoto$ic in a concentration of micrograms!ml, including breast cancers' a(. Synthesi5ed 0=2 derivatives '6H7 , 6H72 and 6H7), also in the comparison of the antitumor activities of vitamin = , =2, and =) against a panel of human cancer cell lines, vitamin =) showed inhibition of various cancers and radioresistant cancers including breast cancer cell lines 'B476 (' in doeses of 2,, +, 2+, and )) micro6J 0= ranged from , to 2 m6, and 0=2 ranged from to 2 m6 in -#+3 values' b(. -n breast cancer, vitamin =) analogue plumbagin e$erted its inhibitor effect in osteoclastogenesis induced by tumor cells and breast cancer7induced osteolytic metastasis through suppression of <A>=; signaling to alter tumor progression'2(. -n breast cancer cell line 64.71, 0=')(, it e$hibited cytoto$icity through #>A fragmentation 'separation or breaking of #>A strands into pieces( and mitochondrial dysfunction')(. -n 64.71, estrogen receptor7positive breast cancer cells, vitamin =) 'menadione( inhibited the transcriptional activity of 1beta7estradiol in a reporter gene assay'*(. 4< 3", a novel vitamin =) derivative, 'S(727'27 hydro$y7)7methylbutylthio(naphthalene7 ,*7dione, e$hibited apoptosis in both the non79&<727overe$pressed 64.71 and 9&<727overe$pressed BT7 *1* breast cancer cells, through induced the loss of mitochondrial membrane

potential, leading to cytochrome c released from mitochondria to cytosol and and cleaved /A</'activate 4>S immune responses( proteins'+(. 6enadione, also known as 0=), its reduction7o$idation, generated by ascorbate7driven menadione redo$ cycling inhibited 64.1 breast cancer cells, through glycolysis'metabolic pathway for generation of energy( inhibition, loss of calcium homeostasis'maintains adeBuate calcium levels(, #>A damage and changes in mitogen activated protein kinases '6A/=( 'regulate proliferation, gene e$pression, differentiation, mitosis, cell survival, and apoptosis ( activities',(. Also, in 64. 1 breast cancer cells, .luorinated 4pd +, an arylating =7vitamin derivative, showed growth inhibition probably via conjugation of cellular thiols, by suppressing the activity of thiol containing cellular protein tyrosine phosphatase '/T/( en5yme'play critical roles in fundamental biological processes(, with conseBuent induction of various tyrosine phosphoproteins'involved in a number of metabolic and signalling pathways( in promoting mutation cell proliferation'1(. 0itamin = although was found effectively in decreased risk and treatment for breast cancers by e$hibition of its effects in cytoto$icity, apoptosis and anti proliferation through #>A fragmentation, mitochondrial dysfunction, cell death pathway, overdoses can induce symptoms of Skin rash, #iarrhea, >ausea, 0omiting, Anemia, etc. /lease make sure you follow the guideline of the -nstitute of 6edicine of the >ational Academies. 4eferences ' ( 4omparison of antitumor activity of vitamins = , =2 and =) on human tumor cells by two '6TT and S<B( cell viability assays by %u .E, ;iao %4, 4hang 96.'/ub6ed( ' a( 0itamin =) inhibition of malignant murine cell growth and human tumor colony formation. by 4hlebowski <T, #ietrich 6, Akman S, Block CB.'/ub6ed( ' b( 0itamin =27derived compounds induce growth inhibition in radioresistant cancer cells by Amalia 9, Sasaki <, Su5uki E, #emi5u E, Bito T, >ishimura 9, ?kamoto E, Eoshida =, 6iyawaki #, =awabe T, 6i5ushina E, Sugimura ='/ub6ed(. '2( /lumbagin inhibits osteoclastogenesis and reduces human breast cancer7 induced osteolytic bone metastasis in mice through suppression of <A>=; signaling by Sung B, ?yajobi B, Aggarwal BB.'/ub6ed( ')( The potential of vitamin =) as an anticancer agent against breast cancer that acts via the mitochondria7related apoptotic pathway by Akiyoshi T,

6at5no S, Sakai 6, ?kamura >, 6atsuyama =.'/ub6ed( '*( Anti7estrogenic activity of fifty chemicals evaluated by in vitro assays by Cung C, -shida =, >ishihara T.'/ub6ed( '+( 4< 3", a novel vitamin =) derivative induces apoptosis and breast tumor inhibition by reactive o$ygen species and mitochondrial dysfunction by Eang 4<, ;iao %S, %u E9, 6urugan =, 4hen 4, 4hao C-.'/ub6ed( ',( 6enadione reduction by pharmacological doses of ascorbate induces an o$idative stress that kills breast cancer cells by Beck <, 0erra$ C, #ejeans >, Taper 9, 4alderon /B.'/ub6ed( '1( :rowth inhibition and protein tyrosine phosphorylation in 64. 1 breast cancer cells by a novel = vitamin by =ar S, 4arr B-.'/ub6ed( 4hinese Secrets To .atty ;iver And ?besity <eversal Mse The <evolutionary .indings To Achieve ?ptimal 9ealth And ;oose %eight ?varian 4ysts And /4?S &limination 9olistic System -n &$istence That %ill Show Eou 9ow To /ermanently &liminate All Types of ?varian 4ysts %ithin 2 6onths Back to <esearched articles 7 /oints of view of 0itamins, .oods and 9erbs httpJ!!kylejnorton.blogspot.ca!p!blog7pagea2*.html Back to =yle C. >orton 9ome page httpJ!!kylejnorton.blogspot.ca All articles written by =yle C. >orton are for information g education only, please consult your #octor g <elated field specialist before applying. 9ealth <esearcher and Article %riter. 6aster in 6athematics and BA in %orld ;iterature and ;iterary criticism.