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.