coumestrol and Ovarian-Neoplasms

Coumestrol, which is predominantly found in soybean products as a phytoestrogen, has cancer preventive activities in estrogen-responsive carcinomas. However, effects and molecular targets of coumestrol have not been reported for epithelial ovarian cancer (EOC). In the present study, we demonstrated that coumestrol inhibited viability and invasion and induced apoptosis of ES2 (clear cell-/serous carcinoma origin) cells. In addition, immunoreactive PCNA and ERBB2, markers of proliferation of ovarian carcinoma, were attenuated in their expression in coumestrol-induced death of ES2 cells. Phosphorylation of AKT, p70S6K, ERK1/2, JNK1/2, and p90RSK was inactivated by coumestrol treatment in a dose- and time-dependent manner as determined in western blot analyses. Moreover, PI3K inhibitors enhanced effects of coumestrol to decrease phosphorylation of AKT, p70S6K, S6, and ERK1/2. Furthermore, coumestrol has strong cancer preventive effects as compared to other conventional chemotherapeutics on proliferation of ES2 cells. In conclusion, coumestrol exerts chemotherapeutic effects via PI3K and ERK1/2 MAPK pathways and is a potentially novel treatment regimen with enhanced chemoprevention activities against progression of EOC.

Topics: Adenocarcinoma, Clear Cell; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Cell Survival; Coumestrol; Cystadenocarcinoma, Serous; Female; Humans; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Neoplasm Invasiveness; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Phytoestrogens; Proliferating Cell Nuclear Antigen; Receptor, ErbB-2

While there is extensive literature evaluating the impact of phytoestrogen consumption on breast cancer risk, its role on ovarian cancer has received little attention.. We conducted a population-based case-control study to evaluate phytoestrogen intake from foods and supplements and epithelial ovarian cancer risk. Cases were identified in six counties in New Jersey through the New Jersey State Cancer Registry. Controls were identified by random digit dialing, CMS (Centers for Medicare and Medicaid Service) lists, and area sampling. A total of 205 cases and 390 controls were included in analyses. Unconditional logistic regression analyses were conducted to examine associations with total phytoestrogens, as well as isoflavones (daidzein, genistein, formononetin, and glycitein), lignans (matairesinol, lariciresinol, pinoresinol, secoisolariciresinol), and coumestrol.. No statistically significant associations were found with any of the phytoestrogens under evaluation. However, there was a suggestion of an inverse association with total phytoestrogen consumption (from foods and supplements), with an odds ratio (OR) of 0.62 (95% CI: 0.38-1.00; p for trend: 0.04) for the highest vs. lowest tertile of consumption, after adjusting for reproductive covariates, age, race, education, BMI, and total energy. Further adjustment for smoking and physical activity attenuated risk estimates (OR: 0.66; 95% CI: 0.41-1.08). There was little evidence of an inverse association for isoflavones, lignans, or coumestrol.. This study provided some suggestion that phytoestrogen consumption may decrease ovarian cancer risk, although results did not reach statistical significance.

Topics: Adult; Carcinoma, Ovarian Epithelial; Case-Control Studies; Confidence Intervals; Coumestrol; Dietary Supplements; Female; Humans; Isoflavones; Lignans; Middle Aged; Neoplasms, Glandular and Epithelial; New Jersey; Odds Ratio; Ovarian Neoplasms; Phytoestrogens; Regression Analysis; Soy Foods; Women's Health