title: Coumestrol suppresses proliferation of ES2 human epithelial ovarian cancer cells.
abstract: 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.
authors.affiliation: Department of BiotechnologyCollege of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of KoreaDepartment of Animal Resources ScienceDankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Whasun
authors.initials: W
authors.lastname: Lim
authors.affiliation: Department of BiotechnologyCollege of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of KoreaDepartment of Animal Resources ScienceDankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Jeong
authors.affiliation: Department of BiotechnologyCollege of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of KoreaDepartment of Animal Resources ScienceDankook University, Cheonan 330-714, Republic of Korea ghsong@korea.ac.kr.
authors.forename: Gwonhwa
authors.initials: G
authors.lastname: Song
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000473:pathology; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003375:Coumestrol / Q000494:pharmacology* / Q000627:therapeutic use; D018284:Cystadenocarcinoma, Serous / Q000473:pathology; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D048789:Phytoestrogens; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D003375:Coumestrol; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D048789:Phytoestrogens; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: clear cell carcinoma; coumestrol; ovary; reproduction; reproductive tract