Ovarian Cancer in Foods, Herbs and Vitamins Points of View

Ovarian Cancer in Foods, Herbs and Vitamins Points of View

By Kyle J. Norton

Ovarian cancer is defined as a condition of abnormal ovarian cells growth of ovaries. It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer, causing 3,850 deaths.Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing invegetables and fruitsin reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some foods have showed to inhibit the progression of cancer with little or no side effects.A. In Foods1.ruciferous vegetablesCruciferous vegetables arethe group of vegetablesbelonging tothe family Brassicaceae, includingcauliflower, cabbage, cress, bok choy, broccoli etc. A meta-analysis of observational studies in reviews of a total of 4,306 cases in 375,562 controls in 11 independent studies indicated a positive effect of consumption of Cruciferous vegetables in a reduced risk of ovarian cancer(1). Isothiocyanates, antioxidants and chemical constituent in cruciferous vegetable, inhibited the cell viability of human ovarian cancer cells, through improved antioxidant status(2). Sulforaphane, SFN the active compound in Isothiocyanates, inhibited the human ovarian cancer cell lines through down-regulate Bcl-2 (a gene involved in anti-apoptosis) protein levels in both cell types and up- regulate thecleaved poly(ADP-ribose) polymerase (PARP)after 6 days of treatment(3). In cell lines MDAH 2774 and SkOV-3, SFN exhibited the suppression of growth in a dose-dependent manner by reduced cell migration and increased apoptotic cell death(4).

2. GarlicGarlic isa natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties. Allium vegetables have been found in many studies to have an inverse association between the frequency of use of and the risk of several common cancers(5). In Human epithelial ovarian cancer cell line A2780, S-allylcysteine (SAC),, an antioxidant and chemical compound extracted from garlic, induced apoptosis through G1/S phase arrest by decreased the proliferative expression and increased expression of active of pro apoptosis(6). In human ovarian cancer cell lines, SAC and SAMC induced apoptosis through activation of E-cadherin(7).

3. GingerGinger (Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil. It has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc. 6-shogaol, a chmeical constituent isolated from ginger showed to inhibited cell growth and modulated secretion of angiogenic factors in ovarian cancer cells, through activation of NF-kappaB and and production of VEGF(stimulation ofvasculogenesis and angiogenesis) and IL-8(Interleukin 8, a chemokine of the immune system)(8). In human A549, SK-OV-3, SK-MEL-2, HCT15 tumor cells and the transgenic mouse ovarian cancer cell lines, 6-shogaol exhibited the most potent cytotoxicityagainst cell proliferation(9).

4. CurcuminTurmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in trditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.Curcumin, a major chemical compound found in turmeric, inhibited the proliferation of both cisplatin-resistant (CR) and sensitive (CS) human ovarian cancer cells through cell cycle arrest, by enhancing the p53 phosphorylation and apoptosis through the activation of caspase-3 followed by PARP degradation(10). E24, a novel curcumin analog, in platinum-sensitive (IGROV1) and platinum-resistant (SK-OV-3) human ovarian cancer cells, in time- and dose-dependently suppressed the growth of both cell lines and synergized with cisplatin to induce apoptosis(11). The Dalhousie University study also showed a positive effect of curcumin ininhibitionof ovarian cancer cell lines independently to p53 but involves p38 MAPK activation, ablation of prosurvival Akt signaling(role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration), and reduced expression of the antiapoptotic proteins Bcl-2 and surviving((baculoviral inhibitor)(12).

5. Tomatos Tomato is a red, edible fruit, genus Solanum, belonging to the family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose and often in green house. In the study conduced by Brigham and Women's Hospital, lycopene found abundantly in tomato, was inversely associated to risk of ovarian cancer, predominantly in premenopausal women(13). and the Loma Linda University study also showedasignificantly reduced risk of all ovarian cancer with higher tomato consumption in comparing intakes > or = five times/week versus never to < 1 time/week(14). But the reviews from FDA's of the scientific data for tomato and/or lycopene intake with respect to risk reduction for certain forms of cancer, found very limited evidence to support an association between tomato consumption and reduced risks of prostate, ovarian, gastric, and pancreatic cancers(15).

6. Red wineRed wine made from anthocyan pigments of the skin of the grapeResveratrol (trans-3,4',5-trihydroxystilbene; RES), a phytoestrogen, existed in grape skin and red wine showed to inhibited on estrogen-dependent ovarian cancer cells proliferation, through cell cycle arrest at the G1 phase andincreased the expression of p21(16). Other researchers suggested that a diet mixed with a dose of 100 mg resveratrol/kg body weight/day for 28 days exhibited effectively in suppressing the in vitro cellular invasion of NuTu-19 ovarian cancer cells(17). The University of Michigan studyindicated the effectiveness of Resveratrol (3,5,4-trihydroxystilbene) ininhibited growth and induced death in a panel of five human ovarian carcinoma cell lines, throughassociation with mitochondrial release of cytochrome c, formation of the apoptosome complex, and caspase activation(18).

7. Organic soybeanSoybean is genus Glycine, the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profit and a healthy foods. Genistein(7-difluoromethoxyl-5,4'-di-n-octyl ), as a major isoflavonoid isolated from dietary soybean, inhibited ovarian cancer cell growth and migration, throughdown-regulated miR-27a expression andsignificantly increased expression of Sprouty2, a putative miR-27a target gene(19) and on bisphenol A (BPA) or 17-estradiol (E2)-induced cell growth and gene alterations of BG-1 ovarian cancer cells expressing estrogen receptors (ERs), GEN(Glycine) effectively suppressed BG-1 cell proliferation promoted by E2 or BPAthrouh inhibiting cell cycle progression and decreased the expression of cyclin D1, a factor responsible for the G1/S cell cycle transition(20). According to the First Affiliated Hospital of Guangzhou Medical college, the derivative 7-difluoromethoxyl-5,4'-di-n-octylgenistein (DFOG), a novel synthetic genistein, was more potent by exerting strongest activity against CoC1 and SKOV3 cells through cell cycle arrest in the G2/M phase and exhibited apoptotic cell death with concomitant attenuation of Forkhead box protein M1 (FoxM1)(a transcriptional activator involved in cell proliferation.)(21).

8. Olive oilOlive is belongs to the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.Accumulations ofevidencesuggested that Olive oil, an integral ingredient of the "Mediterranean diet"may play an important rolein lowering the risk of several types of cancer, including ovarian cancer, through suppressesion ofHER2 at the transcriptional level by up-regulating the expression of the Ets protein PEA3 -a DNA-binding protein that specifically blocks HER2 promoter activity- in ovarian cancer cell lines(22). Data from a multicentre case-control study conducted between 1992 and 1999 in Italy, indicated a protective effectof olive oilagainst ovarian cancer in Italian population(23). Oleic acid, the main olive oil's monounsaturated fatty acid, showed to suppress the overexpression of HER2 (erbB-2), a well know nutation gene in expressionof invasive progression and metastasis in several human cancers, including ovarian cancer(24).

9. Green TeaGreen tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world. Recent study conducted in China also reported that green tea consumption reduced risk of ovarian cancer and increased survival post diagnosis(26)."Green tea consumption suggested to enhance the survival of epithelial ovarian cancer", the cohort comprised 254 patients recruited during 1999-2000 with histopathologically confirmed epithelial ovarian cancer and followed up for a minimum of 3 years said, out of 254, 81 (77.9%) of 104 tea-drinkers who survived to the time of interview, compared to only 67 women (47.9%) still alive among the 140 non-drinkers(27). Epigallocatechin3gallate, phytochemical found in green tea EGCG significantly inhibited the proliferation of OVCAR3 cells in a time and concentrationdependent manner, through increased expression of the activity of p38/MAPK( control of stemness of glioma-initiating cells) and downregulation of the protein expression of MMP2(usually seen in invasive and highly tumorigenic cancers)(28). The study of combination of Epigallocatechin gallate and sulforaphane against paclitaxel-resistant ovarian cancer cells, showed to induced apoptosis of paclitaxel-resistant ovarian cancer cell lines through down-regulating of hTERT(Telomerase reverse transcriptase allows senescent cells that would otherwise become postmitotic and undergo apoptosis) and Bcl-2 and promote DNA damage response(29).

10. Rice branRice bran contains layer between the inner white rice grain and the outer hull. Phytic acid (PA) isolated from rice bran induced marked growth inhibition in ovary, with 50% growth inhibition concentration (IC50)(30). In methanolic extracts from Njavara rice bran, showed to exhibit its anti-proliferative property in C6 glioma cells, possibly through superior antioxidant activity as evidenced by scavenging of free radicals including DPPH and NO(31).

12. AvocadoAvocados 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 Lauraceae. Omega-6 polyunsaturated (n-6) fatty acids found in avocado inhibited the proliferation of ovarian cancer cell(32).

13. Fatty FishFatty fish containing a large amounts of omega-3 fatty acids may be associated to reduced risk of ovarian cancer. High fish intake may be associated with a significantly reduced risk in the 2 case-control studies(33). The Southern Illinois University Carbondale, in hen study indicated that 175 and 700 mg/kg fish oil reduced proliferation and 700 mg/kg increased apoptosis in hen ovaries. may be an effective approach in preventing ovarian carcinogenesis(34).

14. FlaxseedFlax seed is native to the region of the eastern Mediterranean to India and also known as common flax or linseed. Flax is an erect annual plant, it can grow to 1.2 m tall. The leaves are 2040 mm long and 3 mm broad. Omega-3 fatty acids (OM-3FAs) found in flaxseed, showed statistically significant inhibitory effect under the influence of OM-3FAs detected in all four cell lines, (SKOV-3 [p53 null], TOV-21G [wt p53] and OVCAR-3 [mutant p53]) and one immortalized ovarian surface epithelial cell line (IOSE-29)(35). In hens study, flaxseed mediated reduction in the severity of ovarian cancer, correlated to the reduction in PGE2 in the ovaries of flaxseed-fed hens(36). The Southern Illinois University study also indicated the effective of long term flaxseed enriched diet in decreased ovarian cancer incidence and prostaglandin Ein hens(37).

Taking altogether, without going into reviews, the list above has found effectively in reduced risk and treatment of ovarian cancer, but further studies with large example size and multi centers are necessary to identify the principle ingredients to validate the their effectiveness. As always, All articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

References(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M1, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirflt E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martnez Garcia C, Gonzlez CA, Tormo MJ, Quirs JR, Ardanaz E, Larraaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Bchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjnneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A1, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E1, Norat T.(PubMed)(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM1, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)(1) Cruciferous vegetables consumption and the risk of ovarian cancer: a meta-analysis of observational studies by Han B, Li X, Yu T(PubMed)(2) The anti-oxidant properties of isothiocyanates: a review by de Figueiredo SM1, Filho SA, Nogueira-Machado JA, Caligiorne RB.(PubMed)(3) Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation by Chen H1, Landen CN, Li Y, Alvarez RD, Tollefsbol TO(PubMed)(4) Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells by Bryant CS1, Kumar S, Chamala S, Shah J, Pal J, Haider M, Seward S, Qazi AM, Morris R, Semaan A, Shammas MA, Steffes C, Potti RB, Prasad M, Weaver DW, Batchu RB(PubMed).(5) Onion and garlic use and human cancer by Galeone C, Pelucchi C, Levi F, Negri E, Franceschi S, Talamini R, Giacosa A, La Vecchia C.(PubMed)(6) S-allylcysteine, a garlic derivative, suppresses proliferation and induces apoptosis in human ovarian cancer cells in vitro by Xu YS1, Feng JG2, Zhang D3, Zhang B4, Luo M3, Su D5, Lin NM(PubMed)(7) A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through restoration of E-cadherin expression by Chu Q1, Ling MT, Feng H, Cheung HW, Tsao SW, Wang X, Wong YC.(PubMed)(8) Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe by Kim JS1, Lee SI, Park HW, Yang JH, Shin TY, Kim YC, Baek NI, Kim SH, Choi SU, Kwon BM, Leem KH, Jung MY, Kim DK.(PubMed)(9) Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe by Kim JS1, Lee SI, Park HW, Yang JH, Shin TY, Kim YC, Baek NI, Kim SH, Choi SU, Kwon BM, Leem KH, Jung MY, Kim DK.(PubMed)(10) Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK by Weir NM1, Selvendiran K, Kutala VK, Tong L, Vishwanath S, Rajaram M, Tridandapani S, Anant S, Kuppusamy P.(PubMed)(11) Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells by Tan X1, Sidell N, Mancini A, Huang RP, Shenming Wang, Horowitz IR, Liotta DC, Taylor RN, Wieser F.(PubMed)(12) Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling by Watson JL1, Greenshields A, Hill R, Hilchie A, Lee PW, Giacomantonio CA, Hoskin DW.(PubMed)(13) Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women by Cramer DW1, Kuper H, Harlow BL, Titus-Ernstoff L.(PubMed)(14) Dietary risk factors for ovarian cancer: the Adventist Health Study (United States) by Kiani F1, Knutsen S, Singh P, Ursin G, Fraser G.(PubMed)(15) The U.S. Food and Drug Administration's evidence-based review for qualified health claims: tomatoes, lycopene, and cancer by Kavanaugh CJ1, Trumbo PR, Ellwood KC(PubMed)(16) Induced growth of BG-1 ovarian cancer cells by 17-estradiol or various endocrine disrupting chemicals was reversed by resveratrol via downregulation of cell cycle progression by Kang NH1, Hwang KA, Kim TH, Hyun SH, Jeung EB, Choi KC.(PubMed)(17) Resveratrol exerts differential effects in vitro and in vivo against ovarian cancer cells by Stakleff KS1, Sloan T, Blanco D, Marcanthony S, Booth TD, Bishayee A.(PubMed)(18) Resveratrol-induced autophagocytosis in ovarian cancer cells by Opipari AW Jr1, Tan L, Boitano AE, Sorenson DR, Aurora A, Liu JR.(PubMed)(19) Oncogenic MicroRNA-27a is a target for genistein in ovarian cancer cells by Xu L1, Xiang J, Shen J, Zou X, Zhai S, Yin Y, Li P, Wang X, Sun Q.(PubMed)(20) Genistein, a soy phytoestrogen, prevents the growth of BG-1 ovarian cancer cells induced by 17-estradiol or bisphenol A via the inhibition of cell cycle progression by Hwang KA1, Kang NH, Yi BR, Lee HR, Park MA, Choi KC.(PubMed)(21) Apoptosis induced by 7-difluoromethoxyl-5,4'-di-n-octyl genistein via the inactivation of FoxM1 in ovarian cancer cells by Ning Y1, Li Q, Xiang H, Liu F, Cao J.(PubMed)(22) Mediterranean diet, olive oil and cancer by Colomer R1, Menndez JA.(PubMed)(23) Olive oil, seed oils and other added fats in relation to ovarian cancer (Italy) by Bosetti C1, Negri E, Franceschi S, Talamini R, Montella M, Conti E, Lagiou P, Parazzini F, La Vecchia C.(PubMed)(24) Mediterranean dietary traditions for the molecular treatment of human cancer: anti-oncogenic actions of the main olive oil's monounsaturated fatty acid oleic acid (18:1n-9) by Menendez JA1, Lupu R.(PubMed).(25) Green tea consumption enhances survival of epithelial ovarian cancer by Zhang M1, Lee AH, Binns CW, Xie X.(PubMed)(26) Possible role for green tea in ovarian cancer prevention by Lee AH1, Fraser ML, Binns CW.(PubMed)(27) Epigallocatechin3gallate inhibits the proliferation and migration of human ovarian carcinoma cells by modulating p38 kinase and matrix metalloproteinase2 by Wang F, Chang Z, Fan Q, Wang L.(PubMed)(28) Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation by Chen H1, Landen CN, Li Y, Alvarez RD, Tollefsbol TO.(PubMed)(29) Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation by Chen H1, Landen CN, Li Y, Alvarez RD, Tollefsbol TO.(PubMed)(30) Antioxidant and cytotoxicity effect of rice bran phytic acid as an anticancer agent on ovarian, breast and liver cancer cell lines by Norhaizan ME1, Ng SK, Norashareena MS, Abdah MA.(PubMed)(31) The antioxidant and antiproliferative activities of methanolic extracts from Njavara rice bran by Rao AS1, Reddy SG, Babu PP, Reddy AR.(PubMed)(32) Intake of omega-3 and omega-6 fatty acids and risk of ovarian cancer by Ibiebele TI1, Nagle CM, Bain CJ, Webb PM.(PubMed)(33) Meat, fish, and ovarian cancer risk: Results from 2 Australian case-control studies, a systematic review, and meta-analysis by Kolahdooz F1, van der Pols JC, Bain CJ, Marks GC, Hughes MC, Whiteman DC, Webb PM; Australian Cancer Study (Ovarian Cancer) and the Australian Ovarian Cancer Study Group.(PubMed)(34) Anti-inflammatory effects of fish oil in ovaries of laying hens target prostaglandin pathways by Eilati E, Small CC, McGee SR, Kurrey NK, Hales DB1(PubMed)

(35) The effects of Omega-3 fatty acids on growth regulation of epithelial ovarian cancer cell lines by Sharma A1, Belna J, Logan J, Espat J, Hurteau JA(PubMed)(36) Flaxseed enriched diet-mediated reduction in ovarian cancer severity is correlated to the reduction of prostaglandin E(2) in laying hen ovaries by Eilati E1, Hales K, Zhuge Y, Ansenberger Fricano K, Yu R, van Breemen RB, Hales DB(PubMed)(37) Long term consumption of flaxseed enriched diet decreased ovarian cancer incidence and prostaglandin Ein hens by Eilati E1, Bahr JM, Hales DB.(PubMed)B. In Herbs

1. LicoriceLicorice (Glycyrrhiza Glabra) also known as sweetwood, is the genus Glycyrrhiza, belonging to the family Fabaceae, native to the Mediterranean and certain areas of Asia. The herb has been used in traditional medicine to treat skin diseases, coughs, constipation, bronchitis, inflammation, arthritis, etc. Isoliquiritigenin (ISL), a licorice chalconoid, induced apoptosis in ovarian carcinoma SKOV-3 cells and increased intracellular ROS levelsthrough ER stress-triggered signaling pathways, according to Shihezi University(1). 18-glycyrrhetinic acid, another compound found in the same herb, potentiated the effectiveness of Hsp90(heat shock protein 90)in induced apoptosis-related protein activation, nuclear damage, and cell death, through the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated cell death pathway(2). Licochalocone , a natural phenol licorice compounds, enhanced 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a anticancer drugs, in exhibition of apoptosis in human epithelial ovarian carcinoma OVCAR-3 and SK-OV-3 cell lines, through decreasedpro proliferative and increased apoptoticprotein expression(3).

2. Cascara sagrada Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc., effect.Emodin, a chemical compound found in the herb, inhibited drug resistant ovarian tumor growththrough increasing cellular concentration of anti cancer drug paclitaxel and re-sensitizing the resistant cells to paclitaxel(4). The study of the effect of tamoxifen, emodin, and plumbagin in BRCA1(tumor suppressor genes)-blocked ER-positive BG-1 ovarian cancer cells inhibited ovarian cancer cell line througha induced loss of mitochondrial membrane potential (DeltaPsi(m)), nuclear condensation, DNA fragmentation, and morphological changes(5). In human ovarian carcinoma HO-8910PM cell lines, emodin and apigenin, induced cytotoxicity on HO-8910PM cells, throughinhibition oftumor invasion and metastasis(6).

3. Aloe veraAloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.Aloe-emodin, a major compound of herbal Aloe Vera, in composition with Reih exhibited anti human ovarian cancer SK-OV-3, effectin half inhibitory concentration (IC50)(7). Aloe-emodin (AE) alone, showed the effective in significant inhibition of invasion, migration, and adhesion capacities of HO-8910PM cells(human ovarian cancer )(8). Aloin, a natural anthraquinone, extract from Aloe Vera, did not inhibit initiation of DNA synthesis and cells replicated a full complement of DNA but had difficulty in M phase of cell cycle(9).

4. GarlicGarlic isa natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties. Allium vegetables have been found in many studies to have an inverse association between the frequency of use of and the risk of several common cancers(10). In Human epithelial ovarian cancer cell line A2780, S-allylcysteine (SAC),, an antioxidant and chemical compound extracted from garlic, SAC induced apoptosis through G1/S phase arrest by decreased the proliferative expression and increased expression of active of pro apoptosis(11). In other human ovarian cancer cell lines, SAC and SAMC induced apoptosis through activation of E-cadherin(12).

5. GinsengGinseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root). ginsenoside Rg3, a major chemical compound found in Ginseng, inhibited of SKOV-3 cell line through inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9(13).Composition of ginsenoside Rg3 and cyclophosphamide CTX, significantly inhibited growth and angiogenesis of ovarian cancer(14). Ginsenoside Rh2, another chemical compound of the herb, inhibited the cancer cells through induction of apoptosis in addition to augmentation of the natural killer activity in spleen cells from tumor-hearing nude mice(15).

6. Lingzhi (LZ)Ling Zhi is also known as Lucid Ganoderma. The sweet and netral herb has been used in TCM to treat cough, asthma, tinnitus, deafness and lassitude of the loins and knees, palpitation, insomnia and amnesia, hepatitis B, etc. as it nourishes Yin and Blood, strengthens the Spleen tonifies Qi and Body Fluids, calms the Mind, strengthens the Stomach, etc., by enhancing the functions of Lung, Kidney, Liver, Heart, Spleen and Stomach channels.Lingzhi (LZ), also known as Ganoderma lucidum,inhibited the ovarian cancer cell line OVCAR-3, through suppressing cell growth and inducing antioxidative/detoxification activity(16). Other study suggested thatLingZhi also strongly decreased cell numbers in a dose-dependent manner.through inhibition ofcolony formation, cell migration and spheroid formation(17).

7.CranberryCranberry is a evergreen dwarf shrubs, genus Vaccinium, belonging to the family Ericaceae, native to Northern America and Southern Asia. Because of health benefits, it has been cultivated in some parts of the world forcommercial profits and used in traditional and herbal medicine to treat wounds,urinary disorders, diarrhea, diabetes, stomach ailments, and liver problems. Proanthocyanidin (PAC)-rich isolate from cranberry (PAC-1), inhibited ovarian cancer SKOV-3 cell line throughblocked cell cycle progression through the G2/M phase, increased the generation of reactive oxygen species (ROS), and induced apoptosis through activation of intrinsic and extrinsic pathway components(18).Treatment with Proanthocyanidinin SKOV-3 ovarian cancer cells exhibited classic apoptotic changesnd pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value(19).

8. Rosemary Rosemaryis a perennial herb with fragrant, evergreen, needle-like leaves, the genus Rosmarinus, belonging to the family Lamiaceae. Its fresh and dried leaves has been used frequently in traditional Mediterranean cuisine and as flavor foods while barbecuing. Rosnary has been used in traditional medicine as an antiseptic, antioxidant, and antispasmodic agent to treat circulatory problem, eczema, rheumatism, muscle pain, etc.Crude extracts of rosemary (Rosmarinus officinalis L), has been found toconsist anti-proliferative property on several human cancer cell lines and antioxidant and anti-inflammatory properties(20).Carnosol (CS), carnosic acid (CA) and rosmarinic acid (RA), the main ingredients in rosemary extract, exhibited the significant antiproliferation activity on human ovarian cancer A2780 and its CDDP resistant daughter cell line A2780CP70, with IC(50) (50% inhibitory concentration)(21).

9. Devil's Club Devil's Clubis a large shrub, genus Oplopanax, belonging to the family Aralioideae, native to the cool moist forests of western North America. The herb has been used in traditional and herbal medicine as Adaptogen, Antipyretic, Pain Reliever, Antitussive, Antibacterial agent and to treat Arthritis, Diabetes, Colds, Cough, Sore throat, Chest congestion, Stomach pain, Constipation, Gall stones, Influenza, Cancer, etc.Ethanolic extract ofDevil clubdry root bark powder, showed to inhibit the proliferation of some cancer cell lines including K562, HL60, MCF7 and MDA-MB-468 cell growth with the 50% inhibition (IC(50))(22). Water, 70% ethanol, 100% ethanol, and ethyl acetate extracts of OH exhibited significant anti-proliferation effect against both cisplatin sensitive and resistant human ovarian cell lines, including human ovarian cancer cell lines A2780, A2780CP70, OVCAR3, and OVCAR10, according the University of British Columbia(23). In comparison with stem and berry, researchers found that stem extractafter administration of72 h, increased cells apoptosis cells through cell cycle arrest and induction of apoptosis on different human cancer cell lines (SW-480, HCT-116, HT-29, MCF-7 and NSCLC)(24).

10. Ginkgo biloba Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.Ginkgolide B (GB), a major component of Ginkgo biloba extracts, significantly inhibited SKOV3 and CAOV3 cell proliferation by 57.3% and 63.1% compared with control cells with treatment of with 100 M GB for 3 days, through the upregulation of p21(promoted cell cycle arrest), p27(regulation of cell proliferation, cell motility and apoptosis), cleaved capase-3(activated antibody), and cleaved caspase-8(activation and cell death) and downregulation of cyclin D1(regulation of cell cycle progression)(25). In BRCA1 mutations risk of developing ovarian cancers, bioinformatics software analysis indicated that GB treatment involved multiple mechanisms and signal pathways in anticancer activities in BRCA1-mutant cells(26). According to Harvard Medical School,in vitro experiments,Ginkgo extract and its components, quercetin and ginkgolide A and B, have significant anti-proliferative effects ( approximately 40%) in normal and ovarian cancer cells(27).

11. Grape seed extractGrape Seed Extract is the commercial extracts from whole grape seeds that contains many concentrations, including Resveratrol, vitamin E, flavonoids, linoleic acid, oligomeric proanthocyanidins(OPCs), etc..The herb has been used in traditional medicine as antioxidant, anti-inflammatory agents and to treat skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood vessels, lower cholesterol, etc.Resveratrol, a major compound found in grape seed extract showed to prevent Cisplatin-induced EMT in ovarian cancer cells, through increased cell death, and reduced the risk of metastasis(28). The University of Michigan, in the study of the effects of Resveratrol in response of ovarian cancer cells, indicated that Resveratrol inhibits the growth and induces death in a panel of five human ovarian carcinoma cell lines, associated with mitochondrial release of cytochrome c, formation of the apoptosome complex, and caspase activation(29). The Seoul National University suggested that Resveratrol retards the growth of PA-1 cell xenograft and the expression of eEF1A2 (the gene may be critical in the development of ovarian cancer) in athymic nude mice(30).

12. Valerian is a perennial flowering plant, in the genus Valeriana, belonging to the family Valerianaceae, native to Europe and parts of Asia. The herb has been used as a sedative and relaxing agent and to treat the liver, the urinary tract, the digestive tract problem, nerve conditions, etc.IVHD-valtrate, one of the most active Valeriana jatamansi or Indian Valerian derivatives, inhibited the growth and proliferation of the A2780 and OVCAR-3 ovarian cancer cell lines, through G2/M phase arrest and induced apoptosis, and significantly suppressed the growth of A2780 and OVCAR3 xenograft tumors in a dose-dependent manner(31).

13. Phyllanthus niruri L.Phyllanthus niruri L., also known as stonebreaker or seed-under-leaf, is a widespread tropical plant the genus Phyllanthus, belonging to the family Phyllanthaceae, native to to China, India and South/Central America. The herb has been used in folk medicine to treat kidney stones and in Indian medicine which is for problems of the stomach, genitourinary system, liver, kidney and spleen(32). Corilagin, a major chemical constituent from Phyllanthus niruri L., inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey associated with cell cycle arrest at the G2/M stage and enhanced apoptosis(33). Other researchers suggested that Corilagin inhibited into the culture supernatant of all tested ovarian cancer cell lines through blocking the secretion of TGF-(involved in many cellular processes)(34).

15. Thelypteris torresiana (Gaud)Thelypteris torresiana (Gaud) is a species of fernin the genus of Thelypteris, belonging to the family Thelypteridaceae native to China. The herb has been used in traditional Chinese medicine for treatment of treatment of hydropsy and traumatic bleeding (Institute of Botany, 1976; Ding, 1982).The total flavonoid fraction from the roots of M. torresiana shows significant antitumor activity(35). Protoapigenone, a novel flavonoid isolated from the whole plant Thelypteris torresiana (Gaud), exhibited a significant cytotoxicity on human ovarian cancer cells MDAH-2774 and SKOV3 but not on the immortalized non-cancer ovarian epithelial cells HOSE 6-3 and HOSE 11-12, through S and G2/M phases arrest via decreasing the expression of p-Cdk2, Cdk2(the regulatory subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A) and p27Kip1 (CDKN1B).), p-Cyclin B1 and Cyclin B1(activity is restricted to the G1-S phase, and is essential for cell cycle G1/S phase transition). This protein associates with and is regulated by the regulatory subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A) and p27Kip1 (CDKN1B)(36)), as well as increasing the expression of inactive p-Cdc25C(antibody)(37).

Taking altogether, Certain herbs have been found effectively in reduced risk and treatment of ovarian cancer, through cell cycle arrest, up and down regulation of some mechanisms, but large sample size and multi centers studies are necessary to validate the effectiveness of principle ingredients. As always, All articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

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Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca References(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M1, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirflt E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martnez Garcia C, Gonzlez CA, Tormo MJ, Quirs JR, Ardanaz E, Larraaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Bchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjnneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A1, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E1, Norat T.(PubMed)(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM1, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)(1) Involvement of endoplasmic reticulum stress in isoliquiritigenin-induced SKOV-3 cell apoptosis by Yuan X1, Yu B, Wang Y, Jiang J, Liu L, Zhao H, Qi W, Zheng Q.(PubMed)(2) 18-glycyrrhetinic acid potentiates Hsp90 inhibition-induced apoptosis in human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathway by Yang JC1, Myung SC, Kim W, Lee CS(PubMed)(3) Guanylate cyclase activator YC-1 potentiates apoptotic effect of licochalcone A on human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathways by Lee CS1, Kwak SW, Kim YJ, Lee SA, Park ES, Myung SC, Kim W, Lee MS, Lee JJ.(PubMed)(4) Emodin sensitizes paclitaxel-resistant human ovarian cancer cells to paclitaxel-induced apoptosis in vitro by Li J1, Liu P, Mao H, Wanga A, Zhang X.(PubMed)(5) Antisense blocking of BRCA1 enhances sensitivity to plumbagin but not tamoxifen in BG-1 ovarian cancer cells by Srinivas G1, Annab LA, Gopinath G, Banerji A, Srinivas P.(PubMed)(6) [Effect of emodin and apigenin on invasion of human ovarian carcinoma HO-8910PM cells in vitro].[Article in Chinese] by Zhu F1, Liu XG, Liang NC.(PubMed)(7) Synthesis and anti-tumor activity evaluation of rhein-aloe emodin hybrid molecule by Yuan YF1, Hu XY, He Y, Deng JG.(PubMed)(8) Inhibitory effect of aloe-emodin on metastasis potential in HO-8910PM cell line by He TP1, Yan WH, Mo LE, Liang NC.(PubMed)(9) DNA ploidy and S phase fraction of breast and ovarian tumor cells treated with a natural anthracycline analog (aloin) by Esmat AY1, El-Gerzawy SM, Rafaat A.(PubMed)(10) Onion and garlic use and human cancer by Galeone C, Pelucchi C, Levi F, Negri E, Franceschi S, Talamini R, Giacosa A, La Vecchia C.(PubMed)(11) S-allylcysteine, a garlic derivative, suppresses proliferation and induces apoptosis in human ovarian cancer cells in vitro by Xu YS1, Feng JG2, Zhang D3, Zhang B4, Luo M3, Su D5, Lin NM(PubMed)(11) A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through restoration of E-cadherin expression by Chu Q1, Ling MT, Feng H, Cheung HW, Tsao SW, Wang X, Wong YC.(PubMed)(12) Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe by Kim JS1, Lee SI, Park HW, Yang JH, Shin TY, Kim YC, Baek NI, Kim SH, Choi SU, Kwon BM, Leem KH, Jung MY, Kim DK.(PubMed)(13) Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis by Xu TM1, Cui MH, Xin Y, Gu LP, Jiang X, Su MM, Wang DD, Wang WJ.(PubMed)(14) Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer by Xu TM1, Xin Y, Cui MH, Jiang X, Gu LP.(PubMed)(15) Inhibitory effects of ginsenoside Rh2 on tumor growth in nude mice bearing human ovarian cancer cells by Nakata H1, Kikuchi Y, Tode T, Hirata J, Kita T, Ishii K, Kudoh K, Nagata I, Shinomiya N.(PubMed)(16) Suppression of proliferation and oxidative stress by extracts of Ganoderma lucidum in the ovarian cancer cell line OVCAR-3 by Hsieh TC1, Wu JM.(PubMed)(17) Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin by Zhao S1, Ye G, Fu G, Cheng JX, Yang BB, Peng C.(PubMed)(18) Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells by Kim KK1, Singh AP, Singh RK, Demartino A, Brard L, Vorsa N, Lange TS, Moore RG.(PubMed)(19) Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin by Singh AP1, Singh RK, Kim KK, Satyan KS, Nussbaum R, Torres M, Brard L, Vorsa N.(PubMed)(20) Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis.by Cheung S1, Tai J.(PubMed)(21) Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro by Tai J1, Cheung S, Wu M, Hasman D.(PubMed)(22) In vitro anti-proliferative and antioxidant studies on Devil's Club Oplopanax horridus by Tai J1, Cheung S, Cheah S, Chan E, Hasman D.(PubMed)(23) Inhibition of human ovarian cancer cell lines by devil's club Oplopanax horridus by Tai J1, Cheung S, Chan E, Hasman D.(PubMed)(24) High performance liquid chromatographic analysis and anticancer potential of Oplopanax horridus: comparison of stem and berry extracts by Wang CZ1, Aung HH, Mehendale SR, Shoyama Y, Yuan CS.(PubMed)(25) Ginkgo May Sensitize Ovarian Cancer Cells to Cisplatin: Antiproliferative and Apoptosis-Inducing Effects of Ginkgolide B on Ovarian Cancer Cells by Jiang W1, Cong Q, Wang Y, Ye B, Xu C.(PubMed)(26) Ginkgo may prevent genetic-associated ovarian cancer risk: multiple biomarkers and anticancer pathways induced by ginkgolide B in BRCA1-mutant ovarian epithelial cells by Jiang W1, Qiu W, Wang Y, Cong Q, Edwards D, Ye B, Xu C.(PubMed)(27) Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence by Ye B1, Aponte M, Dai Y, Li L, Ho MC, Vitonis A, Edwards D, Huang TN, Cramer DW.(PubMed)(28) Resveratrol Inhibits Cisplatin-Induced Epithelial-to-Mesenchymal Transition in Ovarian Cancer Cell Lines by Baribeau S, Chaudhry P, Parent S, Asselin E.(PubMed)(29) Resveratrol-induced autophagocytosis in ovarian cancer cells by Opipari AW Jr1, Tan L, Boitano AE, Sorenson DR, Aurora A, Liu JR.(PubMed)(30) Resveratrol suppresses growth of human ovarian cancer cells in culture and in a murine xenograft model: eukaryotic elongation factor 1A2 as a potential target by Lee MH1, Choi BY, Kundu JK, Shin YK, Na HK, Surh YJ.(PubMed)(31) Valeriana jatamansi constituent IVHD-valtrate as a novel therapeutic agent to human ovarian cancer: in vitro and in vivo activities and mechanisms.

Li X1, Chen T, Lin S, Zhao J, Chen P, Ba Q, Guo H, Liu Y, Li J, Chu R, Shan L, Zhang W, Wang H.(PubMed)(32) "Keelanelli". Tamilnadu.com. 21 January 2013.

(33) A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF- signaling pathways by Jia L1, Jin H, Zhou J, Chen L, Lu Y, Ming Y, Yu Y.(PubMed)

(34) A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF- signaling pathways by Jia L1, Jin H, Zhou J, Chen L, Lu Y, Ming Y, Yu Y.(PubMed)

(35) In vitro and in vivo antitumor activity of Macrothelypteris torresiana and its acute/subacute oral toxicity by Huang XH1, Xiong PC, Xiong CM, Cai YL, Wei AH, Wang JP, Liang XF, Ruan JL(PubMed)

(36) Bioworld(37) Protoapigenone, a novel flavonoid, inhibits ovarian cancer cell growth in vitro and in vivo by Chang HL1, Su JH, Yeh YT, Lee YC, Chen HM, Wu YC, Yuan SS.(PubMed)

C. In Vitamins

C.1. Vitamin A

Recommended intakes of vitamin A, according to the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 g daily as extremely high doses (>9000 mg) can be toxicity as causes ofdry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc. Epidemiological studies, linking vitamin A in reduced risk and treatment ofovarian cancer have been inclusive(a)(b)(c)(d)(e)(f). 1. RetinolsAccording to Temple University School of Medicine, retinols, the natural and synthetic derivatives of vitamin A, showed to inhibit the growth of human ovarian cancer cells both in vivo and in culture, suppressed ovarian carcinoma cell growth and induced apoptosis in ovarian tumor cells(1). All-trans-retinoic acid (ATRA)has shown to inhibit thegrowth of several ovarian tumor cell lines, other ovarian carcinoma cell lines, and its synthetic version AHPN/CD437 induced apoptosisthrough at least in part via an RAR(retinoic acidreceptor)pathway(2)(3). Other study suggested that a novel combination of ATRA and zoledronic acidsignificantly inducedapoptosis ofrelated cell death in both OVCAR-3 and MDAH-2774 ovarian cancer cell lines with fewer side effects as compared to conventional cytotoxic agents(4).Some researchers suggested that ovarian cancer may be as a result of impaired conversion of retinol to RA in ovarian cancer cells and decreased CRBP1(Cellular Retinol Binding Protein 1) protein expression in prophylactic oophorectomies(surgery that reduces risk of breast cancer and ovarian cancer)causing concomitant losses of vitamin A metabolism and CRBP1 expression of which contribute to ovarian oncogenesis(5). Rb2/p130, a tumor suppressor protein with function in regulation of cell cycle progression, treatment of ATRA in sensitive ovarian carcinoma CA-OV3 cells, showed a dramatic increase in Rb2/p130 protein mediated growth arrest at G0/G1, but not growth arrest, although with a Rb2/p130 expressed at high levels in SK-OV3 cells(6)(7).

2. Carotenoids(beta-carotene, alpha-carotene, gamma-carotene and beta-cryptoxanthin) Carotenoids, plant pigments, converted to vitamin A after intake, play an important role in prevention and treatment of some diseases through it antioxidant effects. Fenretinide (4-HPR), a synthetic retinoid, showed to induce apoptosis through a signaling cascade starting from reactive oxygen species (ROS) generation and involving endoplasmic reticulum (ER) stress response, inducing apoptosis(8) and may be used as a preventive agent in genetic mutation, such as BRCA-1 and 2 mutation carrierscauses of ovarian cancer(9). According to the Medical University of Biaystok, in the study of vitamin A variants in association with ovarian cancer risk, among vitamin A family compounds retinol and carotenoids, but not retinoids, inhibited the growth of cancer cells in dose dependent manner on human ovary endometrioid cancer cell line CRL-11731(10). Other researchers suggested to use antioxidants, including vitamin A variants)with first-line chemotherapy in treatment for ovarian cancer. In 2 case of women with ovarian cancer treatment, antioxidants showed to improve the efficacy of chemotherapy when used in conjunction with first-line chemotherapy(11)(12).

Taking altogether, Vitamin A and its variants may be effective in reduced risk and treatment of ovarian cancer, especially when use conjunction with chemotherapy. As always, overdoses can lead to toxic symptoms. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

References(a) Dietary intake and ovarian cancer risk: a systematic review by Crane TE1, Khulpateea BR, Alberts DS, Basen-Engquist K, Thomson CA.(PubMed)(b) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM1, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)(c) The role of antioxidants and vitamin A in ovarian cancer: results from the Women's Health Initiative by Thomson CA1, Neuhouser ML, Shikany JM, Caan BJ, Monk BJ, Mossavar-Rahmani Y, Sarto G, Parker LM, Modugno F, Anderson GL.(PubMed)(d) A randomized parallel-group dietary study for stages II-IV ovarian cancer survivors by Paxton RJ1, Garcia-Prieto C, Berglund M, Hernandez M, Hajek RA, Handy B, Brown J, Jones LA.(PubMed)(e) Association of dietary vitamin A, carotenoids, and other antioxidants with the risk of ovarian cancer by Tung KH1, Wilkens LR, Wu AH, McDuffie K, Hankin JH, Nomura AM, Kolonel LN, Goodman MT.(PubMed)(f) Identification of carotenoids in ovarian tissue in women by Czeczuga-Semeniuk E1, Wolczynski S.(PubMed)(1) Retinoids and ovarian cancer byZhang D1, Holmes WF, Wu S, Soprano DR, Soprano KJ.(PubMed)(2) Induction of apoptosis in ovarian carcinoma cells by AHPN/CD437 is mediated by retinoic acid receptors by Holmes WF1, Dawson MI, Soprano RD, Soprano KJ.(PubMed)(3) All trans retinoic acid and cancer by Siddikuzzaman1, Guruvayoorappan C, Berlin Grace VM.(PubMed)(4) Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: a paradigm of synergistic molecular targeting treatment for ovarian cancer by Karabulut B1, Karaca B, Varol U, Muslu U, Cakar B, Atmaca H, Kisim A, Uzunoglu S, Uslu R.(PubMed)(5) Vitamin A metabolism is impaired in human ovarian cancer by Williams SJ1, Cvetkovic D, Hamilton TC.(PubMed)(6) Characterization of alterations of Rb2/p130 tumor suppressor in all-trans-retinoic acid resistant SK-OV3 ovarian carcinoma cells by Fields AL1, Soprano DR, Soprano KJ.(PubMed)(7) Insulin receptor substrate-1 is an important mediator of ovarian cancer cell growth suppression by all-trans retinoic acid by Ravikumar S1, Perez-Liz G, Del Vale L, Soprano DR, Soprano KJ.(PubMed)(8) AF1q: a novel mediator of basal and 4-HPR-induced apoptosis in ovarian cancer cells by Tiberio P1, Cavadini E, Callari M, Daidone MG, Appierto V(PubMed)(9) Fenretinide (4-HPR): a preventive chance for women at genetic and familial risk? by Cazzaniga M1, Varricchio C, Montefrancesco C, Feroce I, Guerrieri-Gonzaga A.(PubMed)(10) Vitamin A family compounds, estradiol, and docetaxel in proliferation, apoptosis and immunocytochemical profile of human ovary endometrioid cancer cell line CRL-11731 by Czeczuga-Semeniuk E1, Bielawski T, Lemancewicz D, Rusak M, Woczyski S.(PubMed)(11) The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer by Drisko JA1, Chapman J, Hunter VJ.(PubMed)(12) The use of antioxidant therapies during chemotherapy by Drisko JA1, Chapman J, Hunter VJ.(PubMed)

C.2. B Vitamins

C.2.1. Vitamin B6

Vitamin B6, also known as pyridoxine, is a water soluble vitamin found abundantly in green peas, yams, broccoli, asparagus and turnip greens,Peanuts, sunflower seeds, cashews and hazelnuts, meat, fish etc., with functions of amino acid, carbohydrate metabolism, brain health, and liver detoxification, etc.

Epidemiological studies, linking vitamin B6 in reduced risk of ovarian cancer have been inconsistent. The study of the Brigham and Women's Hospital, Boston, indicated that intake of one-carbon metabolism related nutrients, especially vitamin B(6) and methionine, may lower ovarian cancer risk (1). In 80,254 Nurses' Health Study participants, during 22 years of follow-up (1980-2002), researchers found little evidence to support dietary folate, methionine, and vitamin B(6) in related ovarian cancer risk(2), Butin the study to compare the effectiveness of acupuncture plus vitamin B6 PC6 points injection of 142 patients, between March 1, 2006, and June 30, 2008 indicated that acupuncture plus vitamin B6 PC6 points injection relieved nausea and vomiting in patients with ovarian cancer, undergoing a highly emetogenic chemotherapy regimen(3). In a total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) conducted by the Albert Einstein Cancer Center, showed that although administration of pyridoxine significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with cisplatin (DDP) and hexamethylmelamine (HMM) regimens(4). In the assessed dietary intakes and factors associated with diet in women with family history of breast and/or ovarian cancer (FHBOC) study, suggest that women with FHBOC should be encouraged to meet dietary guidelines for cancer prevention, including intake of vitamin B6(5).

Taking altogether, vitamin B6 may be associated to reduced risk and treatment of ovarian cancer when it is used in conjunction with acupuncture, but further study with large sample and multi center studies are necessary to improve the validation. Over dosesmay induced the symptoms ofdifficulty coordinating movement, numbness, sensory changes, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies. References(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M1, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirflt E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martnez Garcia C, Gonzlez CA, Tormo MJ, Quirs JR, Ardanaz E, Larraaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Bchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjnneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A1, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E1, Norat T.(PubMed)(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM1, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)(1)Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR1, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)(2) Intake of folate and related nutrients in relation to risk of epithelial ovarian cancer by Tworoger SS1, Hecht JL, Giovannucci E, Hankinson SE.(PubMed)

(3) Vitamin B6 points PC6 injection during acupuncture can relieve nausea and vomiting in patients with ovarian cancer by You Q1, Yu H, Wu D, Zhang Y, Zheng J, Peng C.(PubMed)(4) Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group by Wiernik PH1, Yeap B, Vogl SE, Kaplan BH, Comis RL, Falkson G, Davis TE, Fazzini E, Cheuvart B, Horton J.(PubMed)(5) Diet and predictors of dietary intakes in women with family history of breast and/or ovarian cancer by McEligot AJ1, Mouttapa M, Ziogas A, Anton-Culver H.(PubMed)

C.2.2. Folate

Folate, also known as folic acid, vitamin B9, is a water soluble vitamin, found abundantly in leafy vegetables, citrus fruits, beans, whole grain, etc. The vitamin plays an important role in synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in certain biological reactions, production of red blood cells for anemia prevention.

Epidemiological studies, focusing folate in reduced risk of ovarian cancer have been inconclusive.Folate, a member of B vitamin plays an important role in DNA synthesis and methylation, may process an anti proliferative effect in ovarain cancer cell lines. The Australian Ovarian Cancer Study (1363 cases, 1414 controls) self-completed risk factor and food-frequency questionnaires, showed a little evidence to support the effect of folate in reduced risk of ovarian cancer(1) and ovarian cancer survival(2). Other researchers suggested that no specific dietary factors are consistently associated with ovarian cancer risk, including folate(3), neither folate intake, MTHFR C677T polymorphism(4) nor one-carbon metabolism(5) A prospective case-control study of the effect of Folic acid and methylenetetrahydrofolate reductase (MTHFR)against ovarian cancersin 215 ovarian cancer patients and 218 controls (all Chinese) between Jan. 2004 and Jan. 2007, indicated a result of a 2.43-fold increased risk of ovarian cancer among MTHFR 677TT carriers, and a decreased risk of ovarian cancer in individuals with high folate intake(6). Intravenous administration of composition of FA-NP showed more potent in anti proliferation than NPagainst both SKOV3 cells and SKOV3/TAX cells, but at the same dose failed to induce apoptosis and inhibit tumor nodule number. Of these results, researchers suggested that the combined use of both FN-NP locally and targetly might prolong the survival time in patients with drug-resistant ovarian cancer(6). The Brigham and Women's Hospital study also supported the evidence of one-carbon metabolism related nutrients, especially vitamin B(7) and methionine inlowering ovarian cancer risk, with a 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008(8).

Taking all together, there are either enough evidencessupported or unsupportedthe effectiveness of folate in reduced risk of ovarian cancer. Further studies with large sample size and mutli centers studies are necessary to clarify the effect of folate in ovarian cancer risk. At the mean time as always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying

References(1) Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer by Webb PM1, Ibiebele TI, Hughes MC, Beesley J, van der Pols JC, Chen X, Nagle CM, Bain CJ, Chenevix-Trench G; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group.(PubMed)(2) Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival by Dixon SC1, Ibiebele TI2, Protani MM1, Beesley J2, Defazio A3, Crandon AJ4, Gard GB5, Rome RM6, Webb PM1, Nagle CM7; on behalf of the Australian Ovarian Cancer Study Group.(PubMed)(3) Dietary intake and ovarian cancer risk: a systematic review, by Crane TE1, Khulpateea BR, Alberts DS, Basen-Engquist K, Thomson CA.(PubMed)(4) Folate intake and MTHFR polymorphism C677T is not associated with ovarian cancer risk: evidence from the meta-analysis by Li C1, Chen P, Hu P, Li M, Li X, Guo H, Li J, Chu R, Zhang W, Wang H.(PubMed)(5) Relationship between dietary and supplemental intake of folate, methionine, vitamin B6 and folate receptor alpha expression in ovarian tumorsby Kotsopoulos J1, Hecht JL, Marotti JD, Kelemen LE, Tworoger SS(PubMed)(6) Folate intake and methylenetetrahydrofolate reductase gene polymorphisms as predictive and prognostic biomarkers for ovarian cancer risk by Zhang L1, Liu W, Hao Q, Bao L, Wang K.(PubMed)(7) Folic acid-coupled nano-paclitaxel liposome reverses drug resistance in SKOV3/TAX ovarian cancer cells by Tong L1, Chen W, Wu J, Li H.(PubMed)(8) Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR1, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)

C.2.3. Vitamin B12

Vitamin B12, also known as cobalamin, a water-soluble 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.

Epidemiological studies, linking vitamin B12 in reduced risk of ovarian cancer have drawn into inconclusive results. Suggestion of Folate, methionine, vitamin B(6) and vitamin B(12) may influence carcinogenesis due to their roles in the one-carbon metabolism pathway. In a study among 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008, have indicated that One-carbon metabolism(metabolic network of interdependent biosynthetic pathways) related nutrients, may lower ovarian cancer risk(1). Nitrosylcobalamin (NO-Cbl), a chemotherapeutic pro-drug derived from vitamin B12 has been found effectively in antiproliferative activity against several human cancer cell lines, including ovarian carcinoma (NIH-OVCAR-3) cells,through induction ofapoptosis via a death receptor/caspase-8 pathway(2). In patients with epithelial ovarian cancer under treatment of Paclitaxel (T) and Carboplatin (J) combination chemotherapy, vitamin B12was effective in relieving symptoms of arthralgia and muscular pain(3).

Taking altogether, vitamin B12 may be effective in reduced riak and treatment of ovarian cancer, but large sample and multu centers studies to validate its effects are necessary. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying. Over doses of the vitamin may induce symptoms of toxicity, including headache, giddiness and abnormal heart functioning, etc., please make sure to follow the guideline of the Institute of Medicine of the National Academies. References(1) Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR1, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)(2) Nitrosylcobalamin promotes cell death via S nitrosylation of Apo2L/TRAIL receptor DR4 by Tang Z1, Bauer JA, Morrison B, Lindner DJ.(PubMed)(3) [The efficacy of Shakuyaku-Kanzo-to for peripheral nerve dysfunction in paclitaxel combination chemotherapy for epithelial ovarian carcinoma].

[Article in Japanese by Fujii K1, Okamoto S, Saitoh K, Sasaki N, Takano M, Tanaka S, Kudoh K, Kita T, Tode T, Kikuchi Y.(PubMed)

C.3. Vitamin C

Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.

The conflict results Epidemiological studies, linking vitamin C in reduced risk of Ovarian cancer have produced inconsistent results. The Robert Wood Johnson Medical School study, indicated a little evidence of an association with dietary TAC or the others individual antioxidants, including vitamin C in reduced risk of epithelial ovarian cancer(1) But the University of Kansas Medical Center, showed a positive effects of vitamin C in inhibition and death in ovarian cancer cells. through multiple pathways. Composition of vitamin C and the conventional chemotherapeutic agents carboplatin, synergistically inhibited ovarian cancer in mouse models and reduced chemotherapy-associated toxicity in patients with ovarian cancer(2) and AA at 250 mol/L showed to completely inhibit serum-stimulated cell proliferation in all cell lines tested, including IOSE-385, OVCAR-3, and OVCA-432 which were was partially (10%-20%) countered by E2 and its metabolites(3). Other researchers suggested that ascorbic acid at the normal plasma concentration has an essential role in maintaining the NK cytotoxicity against ovarian cancer cells in mouse model and depletion of ascorbic acid may impair NK cell activity(4).

The effects Arsenic trioxide (As2O3), a novel compound generated from the oxidation of arsenic routinely, and pharmacological doses of Ascorbic acid(AA), showed to inhibited ovarian cancer cells through manipulation of cellular glutathione (GSH) levels via enhancement of AA's cytotoxicit. These result indicated that depletion of GSH may promote the progression of the disease(5).In in mice bearing glioblastoma xenograft, oral ascorbate administration, exhibited the production of sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood and significantly decreased growth rates of ovarian cancer(6). In human ovarian cancer cell line SK-OV-3, the composition of lysine, proline, arginine, ascorbic acid and green tea extract inhibited the cancer development and invasion, possibly through MMP expression(7). According to American University of the Caribbean, combined treatments of VC (ascorbic acid), VK3 (menadione) on the cellular and nuclear morphology and DNA content of a human ovarian carcinoma cell line (MDAH 2774), showed to inhibit the cancer cell line through generalized DNA degradation(8)(9).

Taking altogether, Vitamin C and its composition may b4 effective in reduced risk and treatment of ovarian cancer through activation of its antioxidant cytotoxicity in enhancement the effectiveness of either novel agents or chemical compounds. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

References(1) Total and individual antioxidant intake and risk of epithelial ovarian cancer by Gifkins D1, Olson SH, Paddock L, King M, Demissie K, Lu SE, Kong AN, Rodriguez-Rodriguez L, Bandera EV.(PubMed)(2) High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy by Ma Y1, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q.(PubMed)(3) Estradiol 17 and its metabolites stimulate cell proliferation and antagonize ascorbic acid-suppressed cell proliferation in human ovarian cancer cells by Li HH1, Zhao YJ, Li Y, Dai CF, Jobe SO, Yang XS, Li XF, Patankar MS, Magness RR, Zheng J.(PubMed)(4) Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model.

Kim JE1, Cho HS, Yang HS, Jung DJ, Hong SW, Hung CF, Lee WJ, Kim D.(PubMed)

(5) Differential augmentative effects of buthionine sulfoximine and ascorbic acid in As2O3-induced ovarian cancer cell death: oxidative stress-independent and -dependent cytotoxic potentiation by Ong PS1, Chan SY, Ho PC.(PubMed)(6) Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice by Chen Q1, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M.(PubMed)(7) Inhibition of matrix metalloproteinase-2 secretion and invasion by human ovarian cancer cell line SK-OV-3 with lysine, proline, arginine, ascorbic acid and green tea extract by Roomi MW1, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M.(PubMed)(8) Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate:menadione treatment. Nuclear and DNA degradation by Gilloteaux J1, Jamison JM, Lorimer HE, Jarjoura D, Taper HS, Calderon PB, Neal DR, Summers JL.(PubMed)(9) The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma by von Gruenigen VE1, Jamison JM, Gilloteaux J, Lorimer HE, Summers M, Pollard RR, Gwin CA, Summers JL.(PubMed)

C.4. Vitamin D

Vitamin D is a fat-soluble 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 zinc.

1. Serum of vitamin D and genes mutationSuggestion of epidemiological studies, linking people who live in higher attitude or carry vitamin D receptor VDR rs2228570 and ApaI polymorphism are associated to the incidence of ovarian cancer and related motility rate(1)(2)(3)(4). These may be due to vitamin D deficiency and genes mutation. According to Uniwersytet Mikoaja Kopernika w Toruniu, [1.25(OH)2D3, the active form of vitamin D showed to inhibit cancer cell growth, induced cancer cell maturation, apoptosis, and decreased angiogenesis. People with lower levels of serum 25-hydroxyvitamin D (25[OH]D) are associated to risk of ovarian cancer development(6)(7), lower overall survival rate and severe deficiency in more aggressive course of ovarian cancer(5). But the Vanderbilt University School of Medicine, in association between circulating 25(OH)D and ovarian cancer risk, in logistic regression models used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls, do not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women(8).

The efficacyEpidemiological studies focusing in vitamin D in reduced risk of ovarian cancer have been inclusive. The study of Brigham and Women's Hospital and Harvard Medical School, in a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up, indicated no evidence to support intake of vitamin D from food or supplements or predicted 25(OH)D levels are associated to risk of ovarian cancer(9) neither Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D(10), nor vitamin D supplementation(11). But according to Dr. Holick MF., Improved vitamin D status is associated to decreased risk for developing several deadly cancers including colon, breast, pancreatic and ovarian cancers(12) and Uniwersytet Mikoaja Kopernika w Toruniu, Vitamin D3 supplementation in moderate doses, many be benefits in decreased risk of developing cancer, including ovarian cancer(13). Some researchers suggested that 1,25-Dihydroxyvitamin D3 suppressed telomerase (a an essential enzyme that counteracts the telomere attrition accompanying DNA replication during cell division) expression and decreased in malignant human ovarian tumors as well as human ovarian cancer cell lines through microRNA(short (20-24 nt) non-coding RNAs are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs.)-498(14)(15). In ovarian epithelial cancers (OCa), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2) VD)(3) induced OCa cell apoptosis through down-regulating telomerase(16). Adding to above findings, The study by University of Hawaii Cancer Center suggested that lifetime vitamin D exposure may be inversely associated with risk of ovarian carcinoma(17).

Taking altogether, serum levels of vitamin D and vitamin D may be associated to reduced risk and treatment of ovarian cancer, through regulation of genes and suppression telomerase expression. Over doses of vitamin D supplement may cause excessive calcium absorption, calcification, Urinary stones etc. please make sure to follow the guideline of the Institute of Medicine of the National Academies.

Back to Researched articles - Points of view of Vitamins, Foods and Herbs http://kylejnorton.blogspot.ca/p/blog-page_24.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca References(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M1, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirflt E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martnez Garcia C, Gonzlez CA, Tormo MJ, Quirs JR, Ardanaz E, Larraaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Bchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjnneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A1, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E1, Norat T.(PubMed)(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM1, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)(1) Vitamin D receptor is a novel drug target for ovarian cancer treatment by Zhang X1, Nicosia SV, Bai W.(PubMed)(2) Systematic review and meta-analysis on vitamin D receptor polymorphisms and cancer risk by Xu Y1, He B, Pan Y, Deng Q, Sun H, Li R, Gao T, Song G, Wang S.(PubMed)(3) Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium by Lurie G1, Wilkens LR, Thompson PJ, Carney ME, Palmieri RT, Pharoah PD, Song H, Hogdall E, Kjaer SK, DiCioccio RA, McGuire V, Whittemore AS, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Goodman MT; Ovarian Cancer Association Consortium.(PubMed)(4) Vitamin D receptor FokI, BsmI, ApaI, and TaqI polymorphisms and susceptibility to ovarian cancer: a meta-analysis by Song GG1, Lee YH.(PubMed)(5) [The role of vitamin D in the carcinogenesis of breast and ovarian cancer].

[Article in Polish by Walentowicz-Sadecka M1, Sadecki P, Walentowicz P, Grabiec M.(

HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/23700865" PubMed)

(6) Casting light on 25-hydroxyvitamin D deficiency in ovarian cancer: a study from the NHANES by Bakhru A1, Mallinger JB, Buckanovich RJ, Griggs JJ.(PubMed)(7) Serum 25-hydroxyvitamin D and the risk of ovarian cancer by Toriola AT1, Surcel HM, Agborsangaya C, Grankvist K, Tuohimaa P, Toniolo P, Lukanova A, Pukkala E, Lehtinen M.(PubMed)

(8) Circulating 25-hydroxyvitamin D and risk of epithelial ovarian cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers by Zheng W1, Danforth KN, Tworoger SS, Goodman MT, Arslan AA, Patel AV, McCullough ML, Weinstein SJ, Kolonel LN, Purdue MP, Shu XO, Snyder K, Steplowski E, Visvanathan K, Yu K, Zeleniuch-Jacquotte A, Gao YT, Hankinson SE, Harvey C, Hayes RB, Henderson BE, Horst RL, Helzlsouer KJ.(PubMed)(9) Surrogates of long-term vitamin d exposure and ovarian cancer risk in two prospective cohort studies by Prescott J1, Bertrand KA, Poole EM, Rosner BA, Tworoger SS.(PubMed)(10) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer by Tworoger SS1, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE.(PubMed)(11) The association of vitamin D supplementation with the risk of cancer in postmenopausal women by Redaniel MT1, Gardner MP, Martin RM, Jeffreys M.(P

HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/24337883" ubMed)(12) Vitamin D, sunlight and cancer connection by Holick MF.(PubMed)(13) [The role of vitamin D in the carcinogenesis of breast and ovarian cancer].

[Article in Polish] by Walentowicz-Sadecka M1, Sadecki P, Walentowicz P, Grabiec M.(PubMed)

(14) MIR498 microRNA 498 [ Homo sapiens (human) ](PubMed)

(15) 1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498 by Kasiappan R1, Shen Z, Tse AK, Jinwal U, Tang J, Lungchukiet P, Sun Y, Kruk P, Nicosia SV, Zhang X, Bai W.(PubMed)

(16) Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase by Jiang F1, Bao J, Li P, Nicosia SV, Bai W.(PubMed)

(17) Cataract and ovarian carcinoma: is the vitamin D hypothesis alive? by Lurie G1, Matsuno RK, Wilkens LR, Thompson PJ, Ollberding NJ, Carney ME, Goodman MT.(PubMed)

C.5. Vitamin E

Vitamin E, a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-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 enzymatic activity, free radical scavenger, etc.

Epidemiological studies, linking serum of vitamin E in the risk of ovarian cancer have produced inconsistent results. Serum levels of vitamin are not associated to ovarian cancer risk, according to Tampere University Central Hospital and (1) but the study by Johns Hopkins University School of Hygiene and Public Health, indicated that the higher serum alpha-tocopherol levels are associated with an increased risk of ovarian cancer but diminished after adjustment for cholesterol(2). Other study suggested that lower alpha-tocopherol concentrations may be associated with the toxicity of chemotherapy(3).

Alpha-TEA , a novel vitamin E analogue found to induce apoptosis a wide variety of epithelial cancer cell types, including breast, prostate, lung, colon, ovarian, cervical, and endometrial in cell culture and inhibit tumor burden and metastasis in a syngeneic mouse mammary tumor model,(4). Other study suggested that vitamin E derivative, vitamin E succinate (VES; RRR-alpha-tocopheryl succinate), and a vitamin E analogue alpha-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, excluding normal human mammary epithelial cells(5). In SK-OV-3 human ovarian adenocarcinoma along with its multi-drug resistant version SK-OV-3-paclitaxel-resistant (TR) cells, combination treatment of vitamin E co-loaded with curcumin and paclitaxel(a mitotic inhibitor) exhibited a three-fold tumor inhibition with each of these cell lines(6). According to the University of Strathclyde, intravenous administration tocotrienol-rich fraction (TRF), showed to exhibit tumor regression and improved animal survival in a murine xenograft model(7). In MDAH2774 human ovarian cancer cells combined treatment of Adenovirus-mediated mda-7 (Ad-mda7) plus VES inhibited tumor progression through activation of two apoptotic extrinsic and intrinsic pathways (specifically Fas expression and cleavage of Bid and caspase-8 and disruption of mitochondrial in activation of downstream capase-9 and caspase-3 via cytochrome C releasE) but not the normal fibroblasts(8). and treatment with Ad-mda7-mediated alone induced apoptosis of human ovarian cancer cells via activation of the Fas-FasL signaling pathway(9).

Taking altogether, vitamin E succinate and analogue may be effective in reduced risk and treatment of ovarian cancer. Large sample size and multi center studies to validate the claims are necessary. Over doses of vitamin E supplement can cause symptoms of blurred vision, weakness, dizziness, nausea, diarrhea, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies. References(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M1, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirflt E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martnez Garcia C, Gonzlez CA, Tormo MJ, Quirs JR, Ardanaz E, Larraaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Bchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjnneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A1, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E1, Norat T.(PubMed)(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM1, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)(1) Serum vitamins A and E and carotene in patients with gynecologic cancer by Heinonen PK1, Kuoppala T, Koskinen T, Punnonen R.(PubMed)(2) Prospective study of serum micronutrients and ovarian cancer by Helzlsouer KJ1, Alberg AJ, Norkus EP, Morris JS, Hoffman SC, Comstock GW.(PubMed)(3) Serum alpha-tocopherol, retinol and neopterin during paclitaxel/carboplatin chemotherapy by Melichar B1, Kalbov H, Krcmov L, Urbnek L, Hyspler R, Malrova E, Solichov D.(Pu

HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/18214051" bMed)(4) Vitamin E and breast cancer by Kline K1, Yu W, Sanders BG.(PubMed)(5) Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA by Anderson K1, Simmons-Menchaca M, Lawson KA, Atkinson J, Sanders BG, Kline K.(PubMed)(6) Polyethylene glycol-phosphatidylethanolamine (PEG-PE)/vitamin E micelles for co-delivery of paclitaxel and curcumin to overcome multi-drug resistance in ovarian cancer by Abouzeid AH1, Patel NR1, Torchilin VP2(PubMed)(7) Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles by Fu JY1, Blatchford DR, Tetley L, Dufs C.(PubMed)(8) Vitamin E succinate in combination with mda-7 results in enhanced human ovarian tumor cell killing through modulation of extrinsic and intrinsic apoptotic pathways by Shanker M1, Gopalan B, Patel S, Bocangel D, Chada S, Ramesh R.(PubMed)(9) Activation of the Fas-FasL signaling pathway by MDA-7/IL-24 kills human ovarian cancer cells by Gopalan B1, Litvak A, Sharma S, Mhashilkar AM, Chada S, Ramesh R.(PubMed)

C.6. Vitamin K

Vitamin K(K1, phylloquinone; K2, menaquinones), is a fat soluble vitamin, foundabundantly inleafy green vegetables, broccoli, and Brussels sprouts, etc. It is best known for promotion of coagulation and bone health.

Researchers at the Showa Universityindicated thatvitamin K may process the anti wide array of human cancer cell lines properties through differentiation and apoptosis(1). DR. Shibayama-Imazu, the leader of the research team said that these inductions may be through interruptionof the morphological changes and DNA fragmentation via the loss of mitochondrial membrane potential (DeltaPsim caused by superoxide(1). Vitamin K2 also induced apoptosis of human ovary cancer cells (TYK-nu cells), through the process of production of superoxide, induced oxidative stress in mitochondria might damage mitochondrial membranes(2). In PA-1 ovarian cancer cells, vitamin exhibited apoptosis through increased in the synthesis of TR3 and the accumulation of TR3 in mitochondria and in nucleivia a JNK signaling pathway(3). Against human ovarian carcinoma cell line (MDAH 2774), the composition of VC (ascorbic acid) andVK3 (menadione), inhibited cell proliferation through DNA degradation(4) andexposure to the composition also expressed the anti proliferation of cell death through autoschizis (43%), apoptosis (3%), and oncosis (1.9%)(5). In the comparison of the effect of vitamin K(2) (menaquinone 4) and geranylgeraniol (GGO)inhuman cancer cell line, showed that GGO inhibited the growth of all eight cell lines derived from solid tumors, while vitamin K(2) selectively inhibited the proliferation and induced apoptosisin both ovarian cell lines(6). Study of the cytotoxic effect and mechanism of action of vitamins C (VC) and K3 (VK3) on ovarian carcinoma, indicated a positive effects of the composition in induced cell death (displayed characteristics of both apoptosis and necrosis), through cycle arrest and degradation of chromosomal DNA(7).

Taking all together, vitamin VK2 and VK3 are found effectively in reduced risk and treatment of ovarian cancer through activation of cell death mechanism, via activation of RSO, cell cycle arrest, and inhibition of cell proliferation via degradationof DNA. Large sample and multi centers studies to validate this effectiveness are necessary. Overdoses can induce symptoms of Skin rash, Diarrhea, Nausea, Vomiting, Anemia, etc. Please make sure you follow the guideline of the Institute of Medicine of the National Academies

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Back to Researched articles - Points of view of Vitamins, Foods and Herbs http://kylejnorton.blogspot.ca/p/blog-page_24.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca References(1) Vitamin K2-mediated apoptosis in cancer cells: role of mitochondrial transmembrane potential. by Shibayama-Imazu T1, Aiuchi T, Nakaya K.(PubMed)(2) Production of superoxide and dissipation of mitochondrial transmembrane potential by vitamin K2 trigger apoptosis in human ovarian cancer TYK-nu cells by Shibayama-Imazu T1, Sonoda I, Sakairi S, Aiuchi T, Ann WW, Nakajo S, Itabe H, Nakaya K.(PubMed)(3) Induction of apoptosis in PA-1 ovarian cancer cells by vitamin K2 is associated with an increase in the level of TR3/Nur77 and its accumulation in mitochondria and nuclei by Sibayama-Imazu T1, Fujisawa Y, Masuda Y, Aiuchi T, Nakajo S, Itabe H, Nakaya K.(PubMed)(4) Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate:menadione treatment. Nuclear and DNA degradation by Gilloteaux J1, Jamison JM, Lorimer HE, Jarjoura D, Taper HS, Calderon PB, Neal DR, Summers JL.(PubMed)(5) Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774) cells following vitamin C, vitamin K3 or vitamin C:K3 treatment by Gilloteaux J1, Jamison JM, Arnold D, Taper HS, Von Gruenigen VE, Summers JL.(PubMed)(6) Vitamin K(2) selectively induced apoptosis in ovarian TYK-nu and pancreatic MIA PaCa-2 cells out of eight solid tumor cell lines through a mechanism different from geranylgeraniol by Shibayama-Imazu T1, Sakairi S, Watanabe A, Aiuchi T, Nakajo S, Nakaya K.(PubMed)(7) The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma by von Gruenigen VE1, Jamison JM, Gilloteaux J, Lorimer HE, Summers M, Pollard RR, Gwin CA, Summers JL.(PubMed)

All articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying