Ovarian Cancer in Vitamin E Points of View

By Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovarian cells,  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 were diagnosed with ovarian cancer and 13,850 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 in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some herbs have showed to inhibit the progression of cancer with little or no side effects.

 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.


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months 

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, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner 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, Tjønneland 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, Kalábová H, Krcmová L, Urbánek L, Hyspler R, Malírova E, Solichová D.(PubMed)
(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, Dufès 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)

Ovarian cancer in vitamin A points of view

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 national cancer institute, in 2013 Us alone, 22,240 women were diagnosed with the incidence of the disease with death of 14030.
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. 
Recommended intakes of vitamin A, according to  the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.
Epidemiological studies, linking vitamin A in reduced risk and treatment of ovarian cancer have been inclusive(a)(b)(c)(d)(e)(f).
1. Retinols
According 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 the growth of several ovarian tumor cell lines, other ovarian carcinoma cell lines, and its synthetic version AHPN/CD437 induced apoptosis through at least in part via an RAR(retinoic acid receptor) pathway(2)(3). Other study suggested that a novel combination of ATRA and zoledronic acid significantly induced apoptosis of related 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 carriers causes of ovarian cancer(9). According to the Medical University of Białystok, 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.  


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

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) 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, Wołczyński 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)

Ovarian Cancer in Vitamin D Points of View

Kyle J. Norton

According to the information of national cancer institute, in 2013 Us alone. 22,240 women were diagnosed with the incidence of the disease with death of 14030.
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 in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some herbs have showed to inhibit the progression of cancer with little or no side effects.
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 mutation
Suggestion 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 Mikołaja 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 efficacy
Epidemiological 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 Mikołaja 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.



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

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, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner 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, Tjønneland 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-Sadłecka M¹, Sadłecki P, Walentowicz P, Grabiec M.(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.(PubMed)
(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-Sadłecka M¹, Sadłecki 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)

Polycystic kidney disease in Herbs Points of View

Kyle J. Norton

Polycystic kidney disease, also known as polycystic kidney syndrome is a cystic genetic disorder (a)(b)(c) of the kidneys, classified into:
A. Autosomal dominant polycystic kidney disease (ADPKD) affects all ethnic groups with a prevalence of 1:400-1:1000 live births. The disease induced formation of  numerous cysts in the kidneys with progressively expand and eventually destroy normal kidney structure and function. And may be associated to other disease complications(1)
B. Autosomal recessive polycystic kidney disease (ARPKD) is genetic disorder due to mutation of gene in chromosomal locus 6p12.2., causing up to 50% of affected neonates die of pulmonary hypoplasia and specific changes in the kidney and liver. Children who survive neonatal period (from birth to 28 days of age)may be experience with decrease in kidney size (not affect the kidney function) and change in echogenicity occurs, producing a pattern similar to patients with autosomal dominant polycystic kidney disease(2).
Although the disease is due to gene mutation, according to the study by the West Virginia University, certain phytochemicals in foods and herbs have found effectively in  to attenuation of cyst pathogenesis in animal studies(3).

1. Thunder God Vine (Lei Gong Teng)
Lei Gong Teng is also known as Thunder god vine. The bitter and very toxic herb has been used in TCM as an anti-inflammatiory and immunosuppressive agent and to resolve toxins, treat proteinuric renal disease, etc., as it expels Wind-Damp, resolves edema, calms pain, etc., by enhancing the functions of Liver and kidney channels.
Triptolide, is a diterpenoid epoxide found in the Thunder God Vine or Tripterygium wilfordii. according to the study at Yale University, daily injections of a model of ADPKD with triptolide beginning on Day P16 significantly reduced the total number of cysts per kidney, with a pronounced effect on the number of microcysts and the overall cystic burden. At P22 and P35, the chemical compound also improve blood urea nitrogen levels(4),  renal function at postnatal day 8 by inhibition of the early phases of cyst growth(5).

2. Turmeric
Turmeric 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 constituent found in turmeric, showed a profound effect in inhibition of  cyst progression, by improved renal histology and reduced STAT3 activation, proliferation index, cystic index, and kidney weight/body weight ratios, as well as significantly postponed renal failure in mice with severe PKD(6). Other study at the Peking University, showed to inhibit renal cyst formation through inhibited forskolin-promoted cell proliferation and promoted the tubule formation in MDCK (Madin-Darby canine kidney) cells(a possible tool for assessing the membrane permeability properties of early drug discovery compounds), which indicates curcumin promotes MDCK cell differentiation(7). Berberine, another chemical compound found in turmeric and palnts in berberis family exerted its AMP-activated kinase (AMPK) property in suppression of the over expression of rapamycin (mTOR) and cystic fibrosis transmembrane conductance regulator (CFTR) in patients with Polycystic kidney disease(8)(9).

3. 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, a major chemical constituent of Ginkgo biloba, significantly inhibited MDCK cyst formation dose dependently and cyst enlargement in the MDCK cyst model, embryonic kidney cyst model, and PKD mouse mode, through induced cyst cell differentiation and altered the Ras/MAPK signaling pathway(10).

4. Stevia rebaudiana Bertoni (Sweetleaf) 
Stevia rebaudiana Bertoni, also known as sweetleaf is agenus of Stevia, belonging to the family  Asteraceae, native to subtropical and tropical regions from western North America to South America.The herb has been used in folk medicine in treating obesity, hypertension and heartburn, and to help lower uric acid levels(11). According to the joint study by the Mahidol University and Yale University School of Medicine, steviol found in Stevia rebaudiana Bertoni, suppressed CFTR and mTOR/S6K expression in renal cyst-lining epithelial cells, through stimulation of AMP-activated protein kinase (AMPK)(12).Other study also showed a positive effect of steviol in Madin-Darby canine kidney (MDCK) cyst enlargement by inhibiting CFTR channel activity and promoting proteasomal-mediated CFTR degradation(13).

5. San Leng
San Leng, a Chines herb, is also known as sparganum stoloniferum buch.-hams. The acrid, bitter and neutral herb has been used in TCM to promote blood clots, inhibit thrombosis, lower the  blood viscosity, etc. as it breaks up the Blood,  eliminates Blood accumulation, moves Qi. calms pain, etc. by enhancing the functions of liver and spleen channels. According to study by University of Alberta, the herb has also been used as a trial drug to treat polycystic kidney disease (PKD) patients in China. A recently study showed a positive effect against Polycystic kidney disease through reduced the proliferation of renal epithelial cells stimulated by epidermal growth factor (EGF), and inhibited the phosphorylation of the EGF receptor and possibly through inhibition of polycystin-L channel(14).

Taking altogether, the herbs above may be effective in reduced formation of renal cyst, inhibited  progression of the disease in patients with Polycystic kidney disease through some mechanisms, but large sample size and multi centers studies to identify the principle ingredients to validate these effectiveness 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.


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

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) Loss of Polycystin-1 Inhibits Bicc1 Expression during Mouse Development by Lian P¹, Li A¹, Li Y², Liu H², Liang D³, Hu B³, Lin D⁴, Jiang T⁵, Moeckel G⁶, Qin D⁷, Wu G⁸.(PubMed)
(b) Reduced ciliary polycystin-2 in induced pluripotent stem cells from polycystic kidney disease patients with PKD1 mutations by Freedman BS¹, Lam AQ, Sundsbak JL, Iatrino R, Su X, Koon SJ, Wu M, Daheron L, Harris PC, Zhou J, Bonventre JV.(PubMed)
(c) Polycystin-1 but not polycystin-2 deficiency causes upregulation of the mTOR pathway and can be synergistically targeted with rapamycin and metformin by Mekahli D¹, Decuypere JP, Sammels E, Welkenhuyzen K, Schoeber J, Audrezet MP, Corvelyn A, Dechênes G, Ong AC, Wilmer MJ, van den Heuvel L, Bultynck G, Parys JB, Missiaen L, Levtchenko E, De Smedt H.(PubMed)
(1) Metabolic abnormalities in autosomal dominant polycystic kidney disease by Mao Z¹, Xie G, Ong AC.(PubMed)
(2)  decrease in kidney size and change in echogenicity occurs, producing a pattern that is similar to that seen on sonograms of patients with autosomal dominant polycystic kidney disease by Blickman JG¹, Bramson RT, Herrin JT.(PubMed)
(3) Evidence for a role of proteins, lipids, and phytochemicals in the prevention of polycystic kidney disease progression and severity by Maditz KH¹, Gigliotti JC, Tou JC.(PubMed)
(4) Triptolide reduces cyst formation in a neonatal to adult transition Pkd1 model of ADPKD by Leuenroth SJ¹, Bencivenga N, Chahboune H, Hyder F, Crews CM.(PubMed)
(5) Triptolide reduces cystogenesis in a model of ADPKD by Leuenroth SJ¹, Bencivenga N, Igarashi P, Somlo S, Crews CM(PubMed)
(6) Curcumin inhibits cystogenesis by simultaneous interference of multiple signaling pathways: in vivo evidence from a Pkd1-deletion model by Leonhard WN¹, van der Wal A, Novalic Z, Kunnen SJ, Gansevoort RT, Breuning MH, de Heer E, Peters DJ.(PubMed)
(7) Curcumin inhibits renal cyst formation and enlargement in vitro by regulating intracellular signaling pathways by Gao J¹, Zhou H, Lei T, Zhou L, Li W, Li X, Yang B.(PubMed)
(7a) Activation of AMP-activated kinase as a strategy for managing autosomal dominant polycystic kidney disease by McCarty MF¹, Barroso-Aranda J, Contreras F.(PubMed)
(7b) Berberine slows cell growth in autosomal dominant polycystic kidney disease cells by Bonon A¹, Mangolini A, Pinton P, Del Senno L, Aguiari G.(PubMed)
(10) Ginkgolide B inhibits renal cyst development in in vitro and in vivo cyst models by Zhou H¹, Gao J, Zhou L, Li X, Li W, Li X, Xia Y, Yang B.(PubMed)
(11) Tanvir, Ashraf (24 May 2005). "Sugar Leav – A new breed of 'sweetener'". Pakistan Agricultural Research Council. Retrieved 2 January 2009.
(12) Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease by Yuajit C¹, Muanprasat C², Gallagher AR³, Fedeles SV³, Kittayaruksakul S⁴, Homvisasevongsa S⁵, Somlo S⁶, Chatsudthipong V⁷.(PubMed)
(13) Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation by Yuajit C¹, Homvisasevongsa S, Chatsudthipong L, Soodvilai S, Muanprasat C, Chatsudthipong V.(PubMed)
(14) Inhibition of polycystin-L channel by the Chinese herb Sparganum stoloniferum Buch.-Ham by Li F¹, Dai XQ, Li Q, Wu Y, Chen XZ.(PubMed)

Polycystic kidney disease in Foods' Points of View

By Kyle J. Norton

Polycystic kidney disease, also known as polycystic kidney syndrome is a cystic genetic disorder(a)(b)(c) of the kidneys, classified into:
A. Autosomal dominant polycystic kidney disease (ADPKD) affects all ethnic groups with a prevalence of 1:400-1:1000 live births. The disease induced formation of  numerous cysts in the kidneys with progressively expand and eventually destroy normal kidney structure and function. And may be associated to other disease complications(1)
B. Autosomal recessive polycystic kidney disease (ARPKD) is genetic disorder due to mutation of gene in chromosomal locus 6p12.2., causing up to 50% of affected neonates die of pulmonary hypoplasia and specific changes in the kidney and liver. Children who survive neonatal period (from birth to 28 days of age)may be experience with decrease in kidney size (not affect the kidney function) and change in echogenicity occurs, producing a pattern similar to patients with autosomal dominant polycystic kidney disease(2).
Although the disease is due to gene mutation, according to the study by the West Virginia University, certain phytochemicals in foods and herbs have found effectively in attenuation of cyst pathogenesis in animal studies(3).

1. Dietary Flax seeds
Flax 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 20–40 mm long and 3 mm broad. According to the study by the University of Manitoba, Han:SPRD-cy rats fed flaxseed, showed to preserve renal function and reduce histologic injury, through tissue retention of succinate and betaine which may have a metabolic role in the reduction of chronic renal injury(4). Other study suggested that flax seed diet alters renal content of polyunsaturated fatty acids and promotes the formation of less inflammatory classes of renal prostanoides(5).

2. Organic soybean
Soybean 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.
Soy protein may be effective in slow progression of renal injury in the Han:SPRD-cy rat, according to the study by theUniversity of Manitoba. The study with Han:SPRD-cy rat, fed with soy protein diet showed to associate with reduced cystic change, epithelial cell proliferation, macrophage infiltration  and fibrosis and prevented a significant elevation in serum creatinine in diseased versus normal animals(6). In Normal (+/+) and affected (cy/+) weanling male and female Han:SPRD-cy rats, soy protein is found to lower IGF-I in +/+ animals, of that supported a role for IGF-I in the pathogenesis of disease in the Han:SPRD-cy rat and an ameliorating role for dietary soy protein(7). Other researchers suggested that isocaloric diets based on 20% casein or 20% heat-treated soy protein at weaning ad libitum for 8 wk, showed a significant effect in  lower serum creatinine (66 vs. 125 mumol/l; P = 0.002), lower urinary ammonium excretion (0.080 vs. 0.173 mmol/kg; P = 0.01), reduced renal cysts, renal fibrosis, macrophage infiltration, renal tubular cell proliferation, and apoptosis(8)

3. Dietary conjugated linoleic acid
Dietary conjugated linoleic acid(CLA) derived from ruminants, found abundantly in diary produces and meats. In  Han:SPRD-cy rat model of polycystic kidney disease (PKD) fed with CLA, showed an reduction of renal production of PGE2, without reduced availability of the precursor fatty acid, AA. Short-term feeding also exhibited significant renal anti-inflammatory and antifibrotic effects(9). Other in the study of Male and female offspring of Han:SPRD-cy heterozygotes fed diets with 0, 1 or 2% CLA isomer mixture for 12 weeks, showed that both CLA diets reduced body fat content in both genders but did not change lean body mass, renal cystic change in female, fibrosis, macrophage infiltration, tissue oxidized LDL content and proliferation of epithelial cells. The study also found significantly increase of serum creatinine in female rat. and with a  significant negative correlation with renal content of the 18:2 c9,t11 isomer and the sum of histologic effects(10).

4. Fish oil
Fish oil containing a large amounts of omega-3 fatty acids may be associated to reduced risk of Polycystic kidney disease.Dietary fish oil (FO) and soy protein (SP) was found to slow Polycystic kidney disease progression in the Han:SPRD-Cy rat model of polycystic kidney disease (PKD), with fish oil through inhibition of both COX and LOX products produced from n-6 fatty acids and increased 3-series prostanoids in both normal and diseased cortex and medulla(11). The Royal Brisbane and Women's Hospital, Brisbane, study showed a potential benefits of omega-3 polyunsaturated fatty acids on the progression of kidney disease and patient survival, as the acids decrease blood pressure, a known accelerant of kidney disease progression(12). But the study at the Kyorin University School of Medicine indicated that Eicosapentaenoic acids (EPA), one of omega3-polyunsaturated fatty acids, show no significant benefits in the testing of non-azotemic patients(13).

Taking altogether, the above list has been found effectively in reduced the progression of inherited Polycystic kidney disease through many different mechanisms. Further studies are necessary to validate theirs effectiveness. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

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) Loss of Polycystin-1 Inhibits Bicc1 Expression during Mouse Development by Lian P¹, Li A¹, Li Y², Liu H², Liang D³, Hu B³, Lin D⁴, Jiang T⁵, Moeckel G⁶, Qin D⁷, Wu G⁸.(PubMed)
(b) Reduced ciliary polycystin-2 in induced pluripotent stem cells from polycystic kidney disease patients with PKD1 mutations by Freedman BS¹, Lam AQ, Sundsbak JL, Iatrino R, Su X, Koon SJ, Wu M, Daheron L, Harris PC, Zhou J, Bonventre JV.(PubMed)
(c) Polycystin-1 but not polycystin-2 deficiency causes upregulation of the mTOR pathway and can be synergistically targeted with rapamycin and metformin by Mekahli D¹, Decuypere JP, Sammels E, Welkenhuyzen K, Schoeber J, Audrezet MP, Corvelyn A, Dechênes G, Ong AC, Wilmer MJ, van den Heuvel L, Bultynck G, Parys JB, Missiaen L, Levtchenko E, De Smedt H.(PubMed)
(1) Metabolic abnormalities in autosomal dominant polycystic kidney disease by Mao Z¹, Xie G, Ong AC.(PubMed)
(2)  decrease in kidney size and change in echogenicity occurs, producing a pattern that is similar to that seen on sonograms of patients with autosomal dominant polycystic kidney disease by Blickman JG¹, Bramson RT, Herrin JT.(PubMed)
(3) Evidence for a role of proteins, lipids, and phytochemicals in the prevention of polycystic kidney disease progression and severity by Maditz KH¹, Gigliotti JC, Tou JC.(PubMed)
(4) The effect of dietary flaxseed supplementation on organic anion and osmolyte content and excretion in rat polycystic kidney disease by Ogborn MR¹, Nitschmann E, Bankovic-Calic N, Buist R, Peeling J(PubMed)
(5) [Effect of a modified low protein and low fat diet on histologic changes and metabolism in kidneys in an experimental model of polycystic kidney disease].[Article in Serbian] by Banković-Calić N¹, Ogbori MR, Nicman E.(PubMed)
(6) Modification of polycystic kidney disease and fatty acid status by soy protein diet by Ogborn MR¹, Nitschmann E, Weiler HA, Bankovic-Calic N.(PubMed)
(7) Dietary soy protein effects on disease and IGF-I in male and female Han:SPRD-cy rats by Aukema HM¹, Housini I.(PubMed)
(8) Soy protein modification of rat polycystic kidney disease by Ogborn MR¹, Bankovic-Calic N, Shoesmith C, Buist R, Peeling J.(PubMed)
(9) Dietary conjugated linoleic acid reduces PGE2 release and interstitial injury in rat polycystic kidney disease by Ogborn MR¹, Nitschmann E, Bankovic-Calic N, Weiler HA, Fitzpatrick-Wong S, Aukema HM.(PubMed)
(10) Dietary conjugated linoleic acid renal benefits and possible toxicity vary with isomer, dose and gender in rat polycystic kidney disease by Ogborn MR¹, Nitschmann E, Goldberg A, Bankovic-Calic N, Weiler HA, Aukema HM.(PubMed)
(11) Renal cyclooxygenase and lipoxygenase products are altered in polycystic kidneys and by dietary soy protein and fish oil treatment in the Han:SPRD-Cy rat by Ibrahim NH¹, Jia Y, Devassy JG, Yamaguchi T, Aukema HM.(PubMed)
(12) Omega-3 polyunsaturated fatty acids in the treatment of kidney disease by Fassett RG¹, Gobe GC, Peake JM, Coombes JS.(PubMed)
(13) he effect of eicosapentaenoic acid on renal function and volume in patients with ADPKD by Higashihara E¹, Nutahara K, Horie S, Muto S, Hosoya T, Hanaoka K, Tuchiya K, Kamura K, Takaichi K, Ubara Y, Itomura M, Hamazaki T.(PubMed)

Ovarian Cancer in Vitamin C Points of View

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 information of national cancer institute, in 2013 Us alone 22,240 women were diagnosed with the incidence of the disease with death of 14030.
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 μmol/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 E2β 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.



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

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) 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 17β 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)

Ovarian Cancer in Herbs' Points of View

  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 and 13,850 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 in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), but some herbs have showed to inhibit the progression of cancer with little or no side effects.

1. Licorice
Licorice (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 levels through ER stress-triggered signaling pathways, according to Shihezi University(1). 18β-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 decreased pro proliferative and increased apoptotic protein 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 growth through 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 through a 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, through inhibition of tumor invasion and metastasis(6).

3. Aloe vera
Aloe 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, effect in 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. Garlic
Garlic is a 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. Ginseng
Ginseng 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 that LingZhi also strongly decreased cell numbers in a dose-dependent manner. through inhibition of colony formation, cell migration and spheroid formation(17).

7. Cranberry
Cranberry 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 through blocked 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 Proanthocyanidin in 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 to consist 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 Club is 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 of Devil club dry 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 extract after administration of 72 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 µM 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 extract
Grape 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-β(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.

Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

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, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner 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, Tjønneland 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) 18β-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-β 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-β 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)