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 discovery of effective ingredients prevention and treatment of breast cancer with little or no side effects have proven difficultly.
According to statistic, the risk of getting invasive breast cancer during life time of a woman is 1/8.
Detection of tumorigenesis through self observation are still the best approach to discover breast cancer in early stage.
But reduction of the mortality at late stage discovered breast cancer has not been accounted, even with extensively modern technology in the field of diagnosis and insurance protection in Western world, needless to say of those countries with poor health care system.
Suggestions of healthy diet with plenty vegetables and fruits(1)(2)(3) accompanied with change of life style(4)(5)(6) may be the only choice for women in reducing risk of the disease.
In fact, certain vegetables(7)(8), fruits(9)(10) and bioactive phytochemicals found in foods(23)(24) and herbs(33)(34) have been found to induce apoptosis and anti proliferation of breast cancer cells by blocking the energy sources to the tumor site and suppressing the promoted cancers genes.
1. Cruciferous vegetables
Cruciferous vegetables are the group of vegetables belongings 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 evidence against breast cancer in preclinical models.
Benzyl isothiocyanate, the derivative of isothiocyanate displayed an significant efficacy in inhibited 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) by suppressing X-linked inhibitor of apoptosis (XIAP) protein expression of cancer cell line MCF-7 and reduced levels of mutations of p53(antigens) protein level(13).
Loss of normal function of p53 gene was associated with over 50% of cancer patients and mutation p53 gene may have an oncogenic potential.
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 cancer cells cycle arrest in the G2(pre-mitotic phase) and M(nuclear division) phase and induced apoptosis/necrosis(14).
I3C used alone also inhibited Her-2breast cancer cell growth in a dose dependent manner as the compound promoted production of Bax(an apoptosis promoter) and decreased expression of Bcl-2(an apoptosis inhibitor) and, thereby, increased the ratio of Bax to Bcl-2 in favoring apoptosis(15).
2. Tomatoes
Tomato is a red, edible fruit, genus Solanum, belongings 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 dependent, 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 /G1phase(interphase together - chromosomes replicate in preparation for cell division) at physiologically achievable concentrations(range) found in human plasma(16)
Lycopene also Inhibited the ER-positive MCF-7 through cell cycle progression, ER-negative MDA-MB-231 cells through G1 phase cell cycle-arrest(17).
Application of lycopene not only restored the GSTP1 expression but also at 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 non cancer 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 exerted a greater inhibition on cell growth in (Human ductal breast epithelial tumor cell line) T47D cells and increased the incidence of cells undergoing apoptosis, in compared to doxorubicin alone(19).
The soluble frarction (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) demonstrated an 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 antibiotic 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) by decreasing the percent of cancer cells in phase G(2)/M and induced apoptotic cell death through stimulated function of Bax protein and p53(cellular tumor antigen) protein expression(22).
Application of 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).
Protein fraction from garlic was effective in inhibiting tumor growth more efficiently than garlic extract in enhancing the CD8(+) T-cell infiltration into the tumor site(24).
5. Spinach
Spinach, an edible flowering plant in the genus Spinacia, belongings to the family of Amaranthaceae, is considered as a healthy plant containing vary vitamins and minerals, native to central and southwestern Asia.
Consuming spinach was found to exhibit 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 but did 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 at 10% reduced progression of in breast cancer in rat model(27).
6. Kelp
Kelps are large seaweeds (algae) growth under shallow in underwater of oceans belongings to the class Phaeophyceae in the order Laminariales, used for food in many cultures.
Laminaria, a brown kelp seaweed containing antibiotic substance, 1-3 beta glucan, was effective in activated host-mediated immune response in prevented 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 the inhibition of breast cell proliferation(30)(31).
7. Chili pepper
Chili pepper is the fruit of plant from the genus Capsicum, belongings to the nightshade family, Solanaceae, 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 inhibited the growth of ER-positive (MCF-7, T47D, BT-474) and ER-negative (SKBR-3, MDA-MB231) breast cancer cell lines, reduced 50% the size of MDA-MB231 breast cancer tumors(32), through inducing cellular apoptosis via a caspase-independent pathway in MCF-7 cells(33).
In the comparison of Dohevanil, researchers found that both vanilloids, precursor of capsaicin and dohevanil inhibited the growth of DNA fragmentation in MCF-7 cells(34).
8. Carrot
Carrot is root vegetable with orange color normally, a sub spices of Daucus carota, belongings 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 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, through apoptotic and anti proliferative activities(36).
The information findings once again emphasized the importance of healthy diet with plenty vegetables and fruits and change of life style in breast caner risk.
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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 cancerMCF-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 cruciferousvegetable 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].
[Article in Chinese] by Wang AH, Zhang LS.(PubMed)
(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 cancerprevention 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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