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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 difficultly. According to statistic, the risk of getting invasive breast cancer during life time of a women is 1/8.. Detections 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 extensively modern technology in the field of diagnosis and insurance protection in Western world, needless to say of counties which have little. Emerged suggestions of healthy diet with plenty vegetables and fruits(1)(2)(3) with change of life style(4)(5)(6) may be the only choice for women in reducing risk of the diseases.
In fact, certain vegetables(7)(8) and fruits(9)(10) 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.
1. Cruciferous vegetables
Cruciferous vegetables are the group of vegetables belonging to the family Brassicaceae, including cauliflower, cabbage, cress, bok choy, broccoli etc.
Isothiocyanate (ITC), one of the major chemical constistuent found in Cruciferous vegetables has been studied extensively over the past three decades with preclinical evidence for the efficacy of various ITCs against cancer in preclinical models. Benzyl isothiocyanate, the derivative of isothiocyanate showed an effectiveness in influencing carcinogen metabolism and signaling pathways relevant to tumor progression and invasion(11) against MDA-MB-231(breast cancer dell line), human breast cancer xenografts(mutation tissues)(12), suppressing X-linked inhibitor of apoptosis (XIAP) protein expression of cancer cell line MCF-7 by knockdown of the p53(antigens) protein level(13).
In Her-2 positive (a most aggressive case of breast cancer), indole-3-carbinol, a naturally occurring compound found in cruciferous vegetables, used combination with paclitaxel (a mitotic inhibitor) synergistically inhibited growth of Her2/neu human breast cancer cells by arresting cancer cells in the G2(pre-mitotic phase) and M(nuclear division) phase and inducting apoptosis/necrosis(14). I3C used alone also inhibited Her-2breast cancer cell growth in a dose dependent manner as the compound up-regulated Bax(an apoptosis promoter), down-regulated Bcl-2(an apoptosis inhibitor) and, thereby, increased the ratio of Bax to Bcl-2 favoring apoptosis(15).
2. Tomatoes
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.
Lycopene, a major carotenoid component of tomato has been known in research community with the property to attenuate the risk of breast cancer. In a time and doses depended, the compound showed an anti-proliferative activity against ER(estrogen receptor)/PR(progesterone receptor) positive MCF-7, HER2-positive SK-BR-3 and triple-negative MDA-MB-468 cell lines by arresting cell cycle at the G0 /G1 phase(interphase together - chromosomes replicate in preparation for cell division) at physiologically achievable concentrations(range) found in human plasma(16) and Inhibition of the ER-positive MCF-7 through the cell cycle progression, ER-negative MDA-MB-231 cells through G1 phase cell cycle-arrest as well as apoptosis(17). There is a report of a lack of GSTP1 expression in untreated MDA-MB-468. Lycopene treatment not only restored the GSTP1 expression but also with 2 microM, once per week for 2 weeks induced demethylation of RARbeta2 (tumor suppressor gene) and the HIN-1(a cell growth inhibitor)) genes in the noncancer MCF10A fibrocystic breast cells(18).
3. Figs
N-hexane insoluble fraction (HIF) found in figs may be lesser known for its efficacy in breast cancer cell suppressive activity. The combination of HIF and doxorubicin showed a greater inhibition on cell growth in (Human ductal breast epithelial tumor cell line) T47D cells and increased the incidence of cells undergoing apoptosis, when compared to exhibited doxorubicin alone(19). The soluble fraction (Ethyl acetate soluble fraction (EASF)) in fig leave was also found to enhance the cytotoxic effect of doxorubicin by changing the inhibition of cell cycle G(2)/M to G(1) phase(20) and Acetone extract of Ficus religosa leaf (FAE) exerted its efficacy in irreversible inhibition of breast cancer cell growth with moderate toxicity by stimulating the loss of mitochondrial membrane potential in multiple breast cancer cell lines and accelerated cell death through the photosensitizing effect(21).
4. Garlic
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties.
Diallyl trisulfide(DAS), a derived organosulfur compounds (OSCs) suppressed the a ratio of viable cells in the culture of (Human breast cancer cell line) MCF-7 and MCF-12a (a non-tumorigenic epithelial cell line) cells respectively by decreasing the percent of cells in phase G(2)/M and inducing apoptotic cell death as a result of up regulating Bax protein and p53(cellular tumor antigen) protein expression(22). DAS 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 anti-cancer agents(23). In the study of a protein fraction from garlic, the fraction was found to be more effective than the augment CD8(+) T-cell infiltration into the tumor site, in inhibiting tumor growth more efficiently than garlic extract in enhancing the CD8(+) T-cell infiltration into the tumor site(24).
5. Spinach
Spinach is an edible flowering plant in the genus Spinacia, belonging to the family of Amaranthaceae and native to central and southwestern Asia. It is considered as a healthy plant containing vary vitamins and minerals.
Consuming spinach may be a significantly protective effect on breast cancer among premenopausal women(25). Eating carrots or spinach more than twice weekly, compared with no intake, was associated with an odds ratio of 0.56 (95% confidence interval 0.34-0.91), but does not distinguish among several potential explanations for the protective association observed between intake of carrots and spinach and risk of breast cancer.(26). It is said that included supplementation of A. gangeticus aqueous extract of red spinach in 5%, 7.5% and 10% in cancer induced rats showed a induction of all tumor marker enzymes especially at 10%.(27).
6. Kelp
Kelps are large seaweeds (algae) growth under shallow in underwater of shallow oceans belonging to the class Phaeophyceae in the order Laminariales, with the thallus is used for food in many cultures. Laminaria, a brown kelp seaweed containing a antibiotic substance, 1-3 beta glucan, was effective in stimulating the host-mediated immune response and suggested of playing a essential role in preventing the initiation of breast cancer(28). Japanese seaweed (Laminaria angustata) extracts was also found to exert its antimutagenic effects in certain breast and colon carcinogen(29). L-tryptophana substances isolated from the kelp rhizoid, may play an important role in in the inhibition of cell proliferation as an suggestion of increased tryptophan degradation occurred in women with early-stage breast cancer(30)(31).
7. Chili peppers
Chili pepper is the fruit of plants from the genus Capsicum, belonging to the nightshade family, Solanaceae. The fruit has been used in human history for spices and cultivated for commercial profits.
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a chemical constituent of chili peppers used in many cultures as anti cancer agent was found to inhibit the growth of ER-positive (MCF-7, T47D, BT-474) and ER-negative (SKBR-3, MDA-MB231) breast cancer cell lines, reducing 50% the size of MDA-MB231 breast cancer tumors(32), inducing cellular apoptosis through a caspase-independent pathway in MCF-7 cells(33). In the comparison of capsaicin and Dohevanil, synthesized from DHA and vanillylamine (precursor to capsaicin), researchers showed that the exhibited effects of both vanilloids and dohevanil in growth inhibition and DNA fragmentation induction in MCF-7 cells, but dohevanil was more potent than capsaicin(34).
8. Carrot
Carrot can grow to 3ft tall. It is root vegetable with orange color normally, a sub spices of Daucus carota, belongs to the family Apiaceae, native to Asian and Europe.
Intake of cruciferous vegetable and carrot are inversely associations with risk of estrogen receptor-negative/progesterone receptor-negative breast cancer(35). Wild carrot or Daucus carota L. ssp. carota (Apiacea) oil extract, used in traditional medicine in Lebanon and in different regions throughout the world was found to inhibit human colon (HT-29, Caco-2) and breast (MCF-7, MDA-MB-231) cancer cell lines, causing significant increase in cell death and decrease in cell proliferation(36).
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1) Intake of specific fruits and vegetables in relation to risk of estrogen receptor-negative breast cancer among postmenopausal women by Fung TT, Chiuve SE, Willett WC, Hankinson SE, Hu FB, Holmes MD.(PubMed)
(2) Fruits, vegetables and breast cancer risk: a systematic review and meta-analysis of prospective studies by Aune D, Chan DS, Vieira AR, Rosenblatt DA, Vieira R, Greenwood DC, Norat T.(PubMed)
(3) Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients.
Freudenheim JL, Marshall JR, Vena JE, Laughlin R, Brasure JR, Swanson MK, Nemoto T, Graham S.(PubMed)
(4) Life style and risk of development of breast and ovarian cancer by Pięta B, Chmaj-Wierzchowska K, Opala T.(PubMed)(5) Epidemiological evidence for a relationship between life events, coping style, and personality factors in the development of breast cancer by Butow PN, Hiller JE, Price MA, Thackway SV, Kricker A, Tennant CC.(PubMed)
(6) Epidemiological correlates of breast cancer in South India by Babu GR, Lakshmi SB, Thiyagarajan JA.(PubMed)
(7) Dietary organic isothiocyanates are cytotoxic in human breast cancer MCF-7 and mammary epithelial MCF-12A cell lines by Tseng E, Scott-Ramsay EA, Morris ME.(PubMed)
(8) Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype by
(9) Extracts of strawberry fruits induce intrinsic pathway of apoptosis in breast cancer cells and inhibits tumor progression in mice.by Somasagara RR, Hegde M, Chiruvella KK, Musini A, Choudhary B, Raghavan SC.(PubMed)
(10) Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro.by Seeram NP, Adams LS, Zhang Y, Lee R, Sand D, Scheuller HS, Heber D.(PubMed)
(11) Benzyl isothiocyanate: double trouble for breast cancer cells by Rao CV.(PubMed)
(12) Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate by Warin R, Xiao D, Arlotti JA, Bommareddy A, Singh SV.(PubMed)
(13) p53-Independent apoptosis by benzyl isothiocyanate in human breast cancer cells is mediated by suppression of XIAP expression by Kim SH, Singh SV.(PubMed)
(14) 3,3'-diindolylmethane and paclitaxel act synergistically to promote apoptosis in HER2/Neu human breast cancer cells by McGuire KP, Ngoubilly N, Neavyn M, Lanza-Jacoby S.(PubMed)
(15) Translocation of Bax to mitochondria induces apoptotic cell death in indole-3-carbinol (I3C) treated breast cancer cells by Rahman KM, Aranha O, Glazyrin A, Chinni SR, Sarkar FH.(PubMed)
(16) Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines by Takeshima M, Ono M, Higuchi T, Chen C, Hara T, Nakano S.(PubMed)
(17) [Effect of lycopene on the proliferation of MCF-7 and MDA-MB-231 cells].
(18) Modulation of gene methylation by genistein or lycopene in breast cancer cells, by King-Batoon A, Leszczynska JM, Klein CB.(PubMed)
(19) Combinational effects of hexane insoluble fraction of Ficus septica Burm. F. and doxorubicin chemotherapy on T47D breast cancer cells by Nugroho AE, Hermawan A, Putri DD, Novika A, Meiyanto E, Kawaichi M.(PubMed)
(20) Synergistic effects of ethyl acetate fraction of Ficus septica Burm. f. and doxorubicin chemotherapy on T47D human breast cancer cell line by Nugroho AE, Hermawan A, Putri D P, Meiyanto E, Hakim L.(PubMed)(21) Bax translocation mediated mitochondrial apoptosis and caspase dependent photosensitizing effect of Ficus religiosa on cancer cells by Haneef J, Parvathy M, Thankayyan R SK, Sithul H, Sreeharshan S.(PubMed)
(22) Garlic constituent diallyl trisulfide induced apoptosis in MCF7 human breast cancer cells by Malki A, El-Saadani M, Sultan AS.(PubMed)
(23) Anticancer effects of garlic and garlic-derived compounds for breast cancer control.
Tsubura A, Lai YC, Kuwata M, Uehara N, Yoshizawa K.(PubMed)
(24) Purif ied Protein Fraction of Garlic Extract Modulates Cellular Immune Response against Breast Transplanted Tumors in BALB/c Mice Model by Ebrahimi M, Mohammad Hassan Z, Mostafaie A, Zare Mehrjardi N, Ghazanfari T.(PubMed)(25) Food sources of phytoestrogens and breast cancer risk in Mexican women by Torres-Sánchez L, López-Carrillo L, López-Cervantes M, Rueda-Neria C, Wolff MS.(PubMed)
(26) Intake of carrots, spinach, and supplements containing vitamin A in relation to risk of breast cancer byLongnecker MP, Newcomb PA, Mittendorf R, Greenberg ER, Willett WC(PubMed)
(27) Potential anticancer effect of red spinach (Amaranthus gangeticus) extract by Sani HA, Rahmat A, Ismail M, Rosli R, Endrini S.(PubMed)
(28) The dietary intake of Laminaria, a brown seaweed, and breast cancer prevention by Teas J.(PubMed)
(29) Effect of Japanese seaweed (Laminaria angustata) extracts on the mutagenicity of 7,12-dimethylbenz[a]anthracene, a breast carcinogen, and of 3,2'-dimethyl-4-aminobiphenyl, a colon and breast carcinogen by Reddy BS, Sharma C, Mathews L.(PubMed)
(30) Indoleamine 2,3-dioxygenase activity and L-tryptophan transport in human breast cancer cells.
Travers MT, Gow IF, Barber MC, Thomson J, Shennan DB.(PubMed)
(31) [Substance isolated from the kelp rhizoid identified as L-tryptophan shows high inhibition of breast cancer].[Article in Japanese] by Takahashi N, Ojika M, Dogasaki C, Nishizawa M, Fukuoka H, Sahara H, Sato N, Mori M, Kikuchi K.(PubMed)
(32) Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer
cells by modulating the EGFR/HER-2 pathway by Thoennissen NH, O'Kelly
J, Lu D, Iwanski GB, La DT, Abbassi S, Leiter A, Karlan B, Mehta R,
Koeffler HP.(PubMed)
(33) Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway by Chou CC, Wu YC, Wang YF, Chou MJ, Kuo SJ, Chen DR.(PubMed)
(34) Apoptosis induction by dohevanil, a DHA substitutive analog of
capsaicin, in MCF-7 cells by Tuoya, Baba N, Shimoishi Y, Murata Y, Tada
M, Koseki M, Takahata K.(PubMed)
(35) Fruit and vegetable intake in relation to risk of breast cancer in the Black Women's Health Study. by Boggs DA, Palmer JR, Wise LA, Spiegelman D, Stampfer MJ, Adams-Campbell LL, Rosenberg L.(PubMed)
(36) The antioxidant and anticancer effects of wild carrot oil extract by Shebaby WN, El-Sibai M, Smith KB, Karam MC, Mroueh M, Daher CF.(PubMed)
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