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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.
Tops 9 fruits for reducing risk of breast cancer
1. Blueberry
Blueberry is a flower plant, belonging to the family Eriaceae and native to Northern America. It can grows from 10 cm to 4 metres tall.
Triple-negative breast cancer TNBC, a cancer does not express the genes for estrogen receptor (ER), progesterone receptor(PR), and HER2(gene) affecting approximately 15% of all caner cases. Female MDA-MB-231 tumor-bearing mice fed with high fat diet with 5% whole blueberry powder (BB), showed an inhibited TNBC and TNBC-related metastasis by reducing inflammation via specific cytokine-driven pathways with generation of an immune response to reduce tumor growth and metastasis(40). In 17β-estradiol-mediated mammary tumorigenesis, 5% blueberry diet, showed to reduce tumor volume and multiplicity significantly, by down regulation of CYP 1A1(enzymes, able to activate compounds with carcinogenic properties) and ER-α (a receptor activated by the sex hormone estrogen)genes expression and also favorable modulation of microRNA (mir-18a and mir-34c) levels in gene regulation(41). Other chemical constituents anthocyanin and an anthocyanin-pyruvic acid adduct extract of blueberry were found to inhibited cancer cell proliferation by acting as cell antiinvasive factors and chemoinhibitors(42).
2. Avocado
Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green-skinned, pear-shaped fruit that ripens after harvesting and native to the Caribbean, Mexico, South America and Central America, belonging to the flowering plant family Lauraceous.
It is suggested that avocado-produced toxin persin may contain a positive anti breast cancer effect(43), Persin selectively induces a G2-M cell cycle arrest and cell death through caspase-dependent pathway(44). Others in the study of the same, persin showed a anti breast cancer effect in both estrogen receptor (ER) and ER-negative breast cancer cells(45).
3. Strawberry
Strawberries is a genius of Fragaria × ananassa belonging to the family Roseaceae. They have been grown all over the world with suitable climate for commercial profits and for health benefits.
Methanolic extract of strawberry (MESB) fruits showed to induced cytotoxicity in cancer cells, irrespective of origin, in a concentration- and time-dependent manner, in the testing against leukaemia (CEM) and breast cancer (T47D) cell lines through Induction of intrinsic pathway of apoptosis by activating p73 (a tumor suppressor) in breast cancer cells, when tumor suppressor gene p53 was mutated(46). Polyphenols, a major chemical component found in strawberry, as an extract, induced cytotoxic with doses of approximately 50 microg/ml, causing a 50% reduction in cell survival in both the normal and the tumour lines, including (MCF-7) breast cancer cell lines(47). In other study, freeze-dried fruits of two strawberry cultivars ethanol extract, strongly inhibited CaSki and SiHa cervical cancer cell lines and MCF-7 and T47-D breast cancer cell lines(48).
4. Pomegranate
Pomegranate is a fruit-bearing small tree, genus Punica, belonging to family Lythraceae, native to Iran but has been cultivated in Asian since ancient time.
Pomegranate extracts and genistein were found to exert their anti cancer effect in growth inhibition of cell proliferation and induction of apoptosis in human breast cancer cells(MCF-7) in doses and time depending manner(49) by downregulated HR genes (a ubiquitous cellular pathway that mediates transfer of genetic information) and increased expression of microRNAs (miRNAs), miR-183 (predicted target RAD50) and miR-24 (regulation of gene expression)(50). Pomegranate fruit extracts (PFEs), in dose-dependent inhibited NF-kB-dependent reporter gene responses associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing RhoC and RhoA protein expression as these genes are associated with tumor cell invasion and metastasis(51).
6. Grapes
Resveratrol, a polyphenolic compound known as a good chemopreventive agent for inhibiting carcinogenesis processes that target the regulators of cell function and DNA replication, found abundantly in grapes, berries and peanuts are associated to reduced risk of breast caner. HS-1793, a synthetic version of the compound induced G2/M(DNA damage checkpoint) arrest in the cell cycle progression in both types of cells and involved in cell-cycle arrest and probably in induction of p53(tumor suppressor gene)-dependent apoptosis in MCF-7 cells(52). Catechin (RQC), 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 AMPK(cellular energy), and inhibited mTOR(mediate cellular responses) signaling in breast cancer cells(53). In Her-2 breast cancer, fox grape seed extract increased the expression of Bax(an apoptosis promoter) and AIF(Apoptosis inducing factor), and decreased total PARP(cellular processes) expression, leading to significant downregulation of Her-2 in MCF-7 cells(54).
7. Pineapple
Pineapple is a species of Ananas Comos, belonging to the family Bromeliaceae and native to southern Brazil and Paraguay. Today it is widely cultivated for commercial uses. Its rich of vitamins and mineral and digesting enzyme bromelin seems to help digestion after a high protein meal. It is a second only to banana as America's most favourite tropical fruit.
Bromelain, a major chemical constituent or herb used in traditional medicine found in pineapple has exerted its anti-metastasis of breast cancer by up regulating the function of c-Jun N-terminal kinase in cell proliferation, differentiation, survival and migration and p38 kinase to cause programmed cell death(56). In GI-101A breast cancer cells, bromelain induced cell death via activation of the apoptosis mechanism, in increased dose-dependent by promoting apoptosis and cytokine processing of caspase-9 and caspase-3 coinciding with elevation of serum CK18 levels(56). In the brMDA-MB-231 mammary carcinoma, oral administration of bromelain increased the reduced bMAK- and MAK-cell activity in cell cycle regulation from 7.8% to 54% (bMAK-cell activity) and from 16% to 47% (MAK-cell activity by stimulating the deficient monocytic cellular cytotoxicity of mammary tumor(57).
8. Apple
Apple is the pomaceous fruit of the apple tree, a species of the rose family Rosaceae. It is one of the most widely cultivated tree fruits originated in Central Asia.
In estrogen-dependent MCF-7 and estrogen-independent MDA-MB-231 breast cancer cell lines, apple phytochemical extracts significantly inhibited cell proliferation in a dose-dependent manner and cell cycle modulation(58). In breast carcinoma Mcf-7 and Mcf-7:Her18 cells, peels of apple was found to be effective in antiproliferation accompanied by a G0-G1 phase arrest in cell cycle of breast cancer cells by a tumor suppressor protein that suppressed the regulation of cell invasion, metastasis, and angiogenesis(59). Study of apple extracts and quercetin 3-beta-d-glucoside combination, also showed to possess the synergistic effect in MCF-7 cell proliferation(60).
9. Orange
Orange is a species of Citrus Sinensis, belonging to the family Rutaceae and native to the Southeast Asia. Orange is round citrus fruits with finely-textured skins, orange in color and one of most popular fruits in the world.
Polymethoxyflavones (PMFs), a chemical compound found in Sweet orange (Citrus sinensis L.) peel, showed to induce Ca(2+)-mediated apoptosis in human breast cancer cells by induced proapoptotic activity(61). D-limonene, another compound in orange peel oil, in rodent studies, also exhibited its chemotherapeutic activity against mammary cells, through the induction of tumor cell apoptosis, tumor redifferentiation, and/or suppression of key proteins of cell growth-regulating (62).
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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)(43) Synthesis and in vitro evaluation of analogues of avocado-produced toxin (+)-(R)-persin in human breast cancer cells by Brooke DG, Shelley EJ, Roberts CG, Denny WA, Sutherland RL, Butt AJ.(PubMed)
(44) A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells by Butt AJ, Roberts CG, Seawright AA, Oelrichs PB, Macleod JK, Liaw TY, Kavallaris M, Somers-Edgar TJ, Lehrbach GM, Watts CK, Sutherland RL.(PubMed)
(45) Synergistic cytotoxicity between tamoxifen and the plant toxin persin in human breast cancer cells is dependent on Bim expression and mediated by modulation of ceramide metabolism by Roberts CG, Gurisik E, Biden TJ, Sutherland RL, Butt AJ.(PubMed)
(46) 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)
(47) Strawberry polyphenols are equally cytotoxic to tumourigenic and normal human breast and prostate cell lines by Weaver J, Briscoe T, Hou M, Goodman C, Kata S, Ross H, McDougall G, Stewart D, Riches A.(PubMed) (48) Anticarcinogenic Activity of Strawberry, Blueberry, and Raspberry Extracts to Breast and Cervical Cancer Cells, by Wedge DE, Meepagala KM, Magee JB, Smith SH, Huang G, Larcom LL.(PubMed)
(49) Anticancer activities of pomegranate extracts and genistein in human breast cancer cells by Jeune MA, Kumi-Diaka J, Brown J.(PubvMed)
(50) Antiproliferative effects of pomegranate extract in MCF-7 breast cancer cells are associated with reduced DNA repair gene expression and induction of double strand breaks by Shirode AB, Kovvuru P, Chittur SV, Henning SM, Heber D, Reliene R.(PubMed)
(51) Pomegranate fruit extract impairs invasion and motility in human breast cancer by Khan GN, Gorin MA, Rosenthal D, Pan Q, Bao LW, Wu ZF, Newman RA, Pawlus AD, Yang P, Lansky EP, Merajver SD.(PubMed)
(52) The effect of grapefruit intake on endogenous serum estrogen levels in postmenopausal women by Monroe KR, Stanczyk FZ, Besinque KH, Pike MC.(PubMed)
(53) HS-1793, a resveratrol analogue, induces cell cycle arrest and apoptotic cell death in human breast cancer cells by Kim JA, Kim DH, Hossain MA, Kim MY, Sung B, Yoon JH, Suh H, Jeong TC, Chung HY, Kim ND.(PubMed)
(54) Grape polyphenols inhibit Akt/mammalian target of rapamycin signaling and potentiate the effects of gefitinib in breast cancer by Castillo-Pichardo L, Dharmawardhane SF.(PubMed)
(55) Suppression of oncoprotein Her-2 and DNA damage after treatment with Flavan-3- ol vitis labrusca extract by Scola G, Fernandes Correia Laurino CC, Menin E, Salvador M.(PubMed)
(56) Bromelain-induced apoptosis in GI-101A breast cancer cells by Dhandayuthapani S, Perez HD, Paroulek A, Chinnakkannu P, Kandalam U, Jaffe M, Rathinavelu A.(PubMed)
(57) Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients by Eckert K, Grabowska E, Stange R, Schneider U, Eschmann K, Maurer HR.(PubMed)
(58) Apple phytochemical extracts inhibit proliferation of estrogen-dependent and estrogen-independent human breast cancer cells through cell cycle modulation by Sun J, Liu RH.(PubMed)
(59) Antiproliferative effects of apple peel extract against cancer cells by Reagan-Shaw S, Eggert D, Mukhtar H, Ahmad N.(PubMed)
(60) Synergistic effect of apple extracts and quercetin 3-beta-d-glucoside combination on antiproliferative activity in MCF-7 human breast cancer cells in vitro by Yang J, Liu RH.(PubMed)
(61) Apoptosis-inducing activity of hydroxylated polymethoxyflavones and polymethoxyflavones from orange peel in human breast cancer cells by Sergeev IN, Ho CT, Li S, Colby J, Dushenkov S.(PubMed)
(62) Monoterpenes in breast cancer chemoprevention by Crowell PL.(PubMed)
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