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Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.
The widespread of prostate cancer, once considered a disease of aging male, now have become major concerns of governments and scientific community in South East Asian with tendency to effect even younger age population. Suggestions emerged of over consuming bad fats in any time in history accompanied with unhealthy diet and life style may be the possible causes of the disease, linking to the economic prosperity over 2 decades. Foods for diseases' management have been prescribed in folk medicine over thousands of year as one of best medicine of nature in preventing and treating diseases, including prostate cancer.
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth with possibility of spreading to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during physical (rectum) exams.
The Fruits for reducing risk of Prostate cancer
1. Mangosteen fruit
Mangosteen fruit, a tropical fruit growth in South East Asia is a tropical evergreen tree originated in the Sunda Islands and the Moluccas of Indonesia.
In 22Rv1 and LNCaP, and prostate epithelial cells (PrECs), standardized mangosteen fruit extract (MFE), showed its inhibited effect by suppressing tumor growth in a xenograft tumor model without causing damage to non-tumorigenic prostate epithelial cell and induced toxicity(46). Polyphenols, the main chemical constituent of the fruit extract also targeted multiple signaling pathways involved in cell cycle modulation and apoptosis in prostate cancer(47). α-Mangostin, a xanthone derived from Polyphenols of mangosteen fruit, targeted cell cycle-related proteins involved in prostate carcinogenesis(48).
2. Long Pepper or Indian long pepper
Used as a spice and seasoning, Long Pepper or Indian long pepper is a flowering vine in the family Piperaceae.
Piperlongumine (PL), a natural alkaloid presented in the fruit of the Long pepper, exerted its effect on prostate cancer by downregulation of Akt downstream signaling(apoptosis, cell proliferation) resulted in decrease of mTORC1 (nutrient/energy)activity and autophagy (cell degradation)stimulation(49). PL also found to induce rapid depletion of the Androgen receptor (AR) in prostate cancer (PC) cells which is an early indication of prostate cancer(50). In human prostate cancer DU145, PC-3 and LNCaP cells, piperine, another an alkaloid from black and long peppers, exhibited anti-proliferative effect in human prostate cancer cells by inducing cell cycle arrest and autophagy(51).
Pomegranates is a fruit-bearing small tree, genus Punica, belonging to family Lythraceae, native to Iran but has been cultivated in Asian since ancient time.
POMx, a omegranate (PE) formula currently approved for clinical trials, effectively inhibited survivin (baculoviral inhibitor), induced apoptosis, retarded the rate of tumor growth in skeleton(52).
Polyphenols, main chemical compounds from pomegranate fruit extracts (PFEs), slightly decreased secretion of matrix metalloproteinase (MMP)-2 but not MMP-9 (expression usually seen in invasive and highly tumorigenic cancers) from both prostate cell lines(53). Other polyphenol derivative, ellagic acid (EA) than to urolithin (UA) converted from Ellagitannins (ETs) from pomegranate juice (PJ), sgnificantly decreased cell proliferation by exhibiting synergism in PC-3 cells(54).
Strawberries is a genius of Fragaria × ananassa belongs to the family Roseaceae. They have been grown all over the world with suitable climate for commercial profits and for health benefits.
Berry juice study, including strawberry, showed to inhibit prostate cancer cell proliferation, not involve caspase-dependent apoptosis, but in cell-cycle arrest, by down-regulation of the expression of cdk4, cdk6, cyclin D1 and cyclin D3(Decrease the proliferative activity (55). In fact major classes of berry phenolics, including anthocyanins, flavonols, flavanols, ellagitannins, gallotannins, proanthocyanidins, and phenolic acids are found to be effective in inhibition the growth of many human cancer cell lines, including prostate (LNCaP) tumor cell lines at concentrations ranging from 25 to 200 micro g/mL.(56). Crude extracts (250 microg/mL) from strawberry and its pure compounds (100 microg/mL)also found to inhibit prostate (LNCaP, DU145) cancer cells(57).
Grape is a woody vines of the genus Vitis, belong to the family Vitaceae, native to southern Turkey.
Fisetin, a chemical compound found in grape inhibited prostate cancer cell lines through downregulation of the PI3K/Akt (anti-apoptosis and increased cell proliferation)and the mTOR(energy sources) pathways(58). Another chemical constituent pterostilbene, in dose-dependent inhibited cellular proliferation, through activation of expression of AMPK(cellular energy homeostasis) and the p53(antigens) but in p53 positive LNCaP cells, pterostilbene blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression and in p53 negative, induced apoptosis in PC3 cells(59). Piceatannol found in grape, exhibited potential anticancer properties by suppressing proliferation of a wide variety of tumor cells, through cell-cycle arrest, upregulation of antibody antigens and apoptotic activity and down-regulation of cancer cell proliferation(60).
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. The tree is originated in Central Asia.
Apple peel extract (APE), exerted its anti cancer effects by significant decreasing in growth and enhancing clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells, through a G0-G1(Cell cycle) phase arrest(61). In the study of Does an apple a day keep the oncologist away? showed an inverse association of apple intake and incidence of cancer(62).
Papaya is a species of Carica Papaya, belongs to the family Caricaceae and native to the tropics of the Americas, and was first cultivated in Mexico and several centuries.
Benzylisothiocyanate (BITC), a solvent of papaya fruit inhibited cancer cell line through induced apoptosis by converging two major pathways: the death receptor mediated extrinsic and the mitochondrial intrinsic pathway(63). In the role of diet, papaya is found effectively (more than 22.7 g/d (50th percentile) in reduced prostate cancer risk by 7.4 (Adjusted OR 7.4 (95% CI 1.17-46.8)(64). Lycopene, a major chemical constituent in tomato, also in papaya, in prospective and retrospective epidemiological studies indicated of an inverse relationship between lycopene intake and prostate cancer risk in vitro and in vivo experiments(65).
Apricot tree is about 8–12 m tall and a trunk up to 40 cm diameter belonging to the family Rosaceae. Apricot is classified with the family of the plum and has yellow to orange, often tinged red on the side which is exposed to the sun.
Ethanolic extracts (30%) of apricot showed to inhibit the growth of PC-3 and LNCaP (Prostate cancer cell lines) cells; induce apoptosis and alter cell kinetics; down regulated ERalpha (estrogen receptor α), ) and PKC-alpha(interaction with the cell membrane) protein, and demonstrate good binding ability to both mouse uterine estrogen receptors and LNCaP human androgen receptors(66).
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.
Whole-blood fatty acids testing indicated that higher intakes of dietary MUFA(monounsaturated fatty) with principal source of dietary avocado intake was inversely related to prostate cancer(67).
Acetone extract of avocado, containing carotenoids and tocopherols showed to inhibit the growth of both androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines in vitro. Incubation of PC-3 cells with the avocado extract led to G(2)/M cell cycle arrest accompanied by an increase in p27(cell cycle inhibitor) protein expression(68).
10. Citrus fruits
Fruits of the genus Citrus, native to southern and southeast Asia, include grapefruit, lemon, orange, etc.
Study of incidence of prostate caner in North India compared to South India, showed a positive decreased risk of increasing dietary consumption of tea, citrus fruits and melon(69). Citrus consumption is associated with reduced all-cancer incidences, according to the study of cancer incidence among 42,470 Japanese adults in the Ohsaki National Health Insurance Cohort(70). Oral administration of Gold Lotion (GL), an extract of multiple varieties of citrus peels containing abundant flavonoid, showed the deduction of both the weights (57%-100% inhibition) and volumes (78%-94% inhibition) of the tumors without any adverse toxicity, accompanied by mechanistic down-regulation of the protein levels of inflammatory enzymes (inducible nitric oxide synthase, iNOS and cyclooxygenase-2, COX-2), metastasis (matrix metallopeptidase-2, MMP-2 and MMP-9), angiogenesis (vascular endothelial growth factor, VEGF), and proliferative molecules, as well as by the induction of apoptosis in prostate tumors(71). Unfortunately, some studies did not show an association between intake of citrus fruits and the risk of prostate cancer(72).
11. Bitter melon
Bitter melon, a extremely bitter fruit, is a tropical and subtropical vine belonging to the family Cucurbitaceae, native in Asia, Africa, and the Caribbean. Treatment of bitter melon extract (BME) in prostate cancer, enhanced Bax expression(involved in p53-mediated apoptosis) and induced PARP(a nuclear protein implicated in DNA repair) cleavage(during apoptosis), delayed the progression to high-grade prostatic intraepithelial neoplasia (precede the development of prostate adenocarcinoma) and displayed approximately 51% reduction of proliferating cell nuclear antigen expression in mice(73). MCP30, from bitter melon seeds induced apoptosis in PIN and PCa cell lines in vitro and suppressed PC-3 growth in vivo with no effect on normal prostate cells(74). Bitter melon leaf extract (BMLE) inhibited the secretion of MMP-2, MMP-9(metastasis) and urokinase plasminogen activator (uPA)(invasion and metastasis) from rat prostate cancer cell line (PLS10)(75).
Ovarian Cysts And PCOS Elimination
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(46) Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract by Li G1, Petiwala SM1, Pierce DR1, Nonn L2, Johnson J(PubMed)
(47) Polyphenols from the mangosteen (Garcinia mangostana) fruit for breast and prostate cancer by Li G, Thomas S, Johnson JJ.(PubMed)
(48) α-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth by Johnson JJ, Petiwala SM, Syed DN, Rasmussen JT, Adhami VM, Siddiqui IA, Kohl AM, Mukhtar H.(PubMed)
(49) Piperlongumine promotes autophagy via inhibition of Akt/mTOR signalling and mediates cancer cell death by Makhov P, Golovine K, Teper E, Kutikov A, Mehrazin R, Corcoran A, Tulin A, Uzzo RG, Kolenko VM.(PubMed)
(50) Piperlongumine induces rapid depletion of the androgen receptor in human prostate cancer cells by Golovine KV, Makhov PB, Teper E, Kutikov A, Canter D, Uzzo RG, Kolenko VM.(PubMed)
(51) Piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy by Ouyang DY, Zeng LH, Pan H, Xu LH, Wang Y, Liu KP, He XH.(PubMed)
(52) Pomegranate extract inhibits the bone metastatic growth of human prostate cancer cells and enhances the in vivo efficacy of docetaxel chemotherapy by Wang Y, Zhang S, Iqbal S, Chen Z, Wang X, Wang YA, Liu D, Bai K, Ritenour C, Kucuk O, Wu D.(PubMed)
(53) Ellagic acid inhibits migration and invasion by prostate cancer cell lines by Pitchakarn P, Chewonarin T, Ogawa K, Suzuki S, Asamoto M, Takahashi S, Shirai T, Limtrakul P.(PubMed)
(54) Pomegranate Juice Metabolites, Ellagic Acid and Urolithin A, Synergistically Inhibit Androgen-Independent Prostate Cancer Cell Growth via Distinct Effects on Cell Cycle Control and Apoptosis by Vicinanza R, Zhang Y, Henning SM, Heber D.(PubMed)
(55) Inhibition of cancer cell proliferation and suppression of TNF-induced activation of NFkappaB by edible berry juice by in D, Blanchette M, Barrette S, Moghrabi A, Béliveau R.(PubMed)
(56)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)
(57)Isolation and identification of strawberry phenolics with antioxidant and human cancer cell antiproliferative properties by Zhang Y, Seeram NP, Lee R, Feng L, Heber D.(PubMed)
(58) Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management by Adhami VM, Syed DN, Khan N, Mukhtar H.(PubMed)
(59) Activation of AMPK by pterostilbene suppresses lipogenesis and cell-cycle progression in p53 positive and negative human prostate cancer cells by Lin VC, Tsai YC, Lin JN, Fan LL, Pan MH, Ho CT, Wu JY, Way TD.(PubMed)
(60) Biological activity of piceatannol: leaving the shadow of resveratrol by Piotrowska H, Kucinska M, Murias M.(PubMed)
(61) Antiproliferative effects of apple peel extract against cancer cells by Reagan-Shaw S, Eggert D, Mukhtar H, Ahmad N.(PubMed)
(62) Does an apple a day keep the oncologist away by Gallus S, Talamini R, Giacosa A, Montella M, Ramazzotti V, Franceschi S, Negri E, La Vecchia C.(PubMed)
(63) Dietary isothiocyanate mediated apoptosis of human cancer cells is associated with Bcl-xL phosphorylation by Basu A, Haldar S.(PubMed)
(64) Roles of diet, lifetime physical activity and oxidative DNA damage in the occurrence of prostate cancer among men in Klang Valley, Malaysia by Shahar S, Shafurah S, Hasan Shaari NS, Rajikan R, Rajab NF, Golkhalkhali B, Zainuddin ZM.(PubMed)
(65) Multitargeted therapy of cancer by lycopene by van Breemen RB, Pajkovic N.(PubMed)
(66) Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo by Shenouda NS, Sakla MS, Newton LG, Besch-Williford C, Greenberg NM, MacDonald RS, Lubahn DB.(PubMed)
(67)Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica by Jackson MD, Walker SP, Simpson-Smith CM, Lindsay CM, Smith G, McFarlane-Anderson N, Bennett FI, Coard KC, Aiken WD, Tulloch T, Paul TJ, Wan RL.(PubMed)
(68)Inhibition of prostate cancer cell growth by an avocado extract: role of lipid-soluble bioactive substances by Lu QY, Arteaga JR, Zhang Q, Huerta S, Go VL, Heber D(PubMed)
(69) A case control study on prostate cancer in Delhi by Tyagi B, Manoharan N, Raina V.(PubMed)
(70) Citrus consumption and cancer incidence: the Ohsaki cohort study by Li WQ, Kuriyama S, Li Q, Nagai M, Hozawa A, Nishino Y, Tsuji I.(PubMed)
(71) Potent anti-cancer effects of citrus peel flavonoids in human prostate xenograft tumors by Lai CS, Li S, Miyauchi Y, Suzawa M, Ho CT, Pan MH.(PubMed)
(72) Citrus fruits intake and prostate cancer risk: a quantitative systematic review by Bae JM, Lee EJ, Guyatt G.(PubMed)
(73) Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model by Ru P, Steele R, Nerurkar PV, Phillips N, Ray RB.(PubMed)
(74) Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cells by Xiong SD, Yu K, Liu XH, Yin LH, Kirschenbaum A, Yao S, Narla G, DiFeo A, Wu JB, Yuan Y, Ho SM, Lam YW, Levine AC.(PubMed)
(75) Momordica charantia leaf extract suppresses rat prostate cancer progression in vitro and in vivo by Pitchakarn P, Ogawa K, Suzuki S, Takahashi S, Asamoto M, Chewonarin T, Limtrakul P, Shirai T.(PubMed)