title: Menadione induces the formation of reactive oxygen species and depletion of GSH-mediated apoptosis and inhibits the FAK-mediated cell invasion.
abstract: Menadione induces apoptosis in tumor cells. However, the mechanism of apoptosis in ovarian cancer cells exposed to menadione is not clear. In addition, it is unclear whether menadione-induced apoptosis is mediated by the depletion of glutathione (GSH) contents that is associated with the formation of reactive oxygen species. Furthermore, the effect of menadione on the invasion and migration of human epithelial ovarian cancer cells has not been studied. Therefore, we investigated the effects of menadione exposure on apoptosis, cell adhesion, and cell migration using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. The results suggest that menadione may induce apoptotic cell death in ovarian carcinoma cell lines by activating the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The apoptotic effect of menadione appears to be mediated by the formation of reactive oxygen species and the depletion of GSH. Menadione inhibited fetal-bovine-serum-induced cell adhesion and migration of OVCAR-3 cells, possibly through the suppression the focal adhesion kinase (FAK)-dependent activation of cytoskeletal-associated components. Therefore, menadione might be beneficial in the treatment of epithelial ovarian adenocarcinoma and combination therapy.
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea.
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.forename: Dong Suep
authors.initials: DS
authors.lastname: Sohn
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D024483:Vitamin K 3 / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D017382:Reactive Oxygen Species; D024483:Vitamin K 3; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D005978:Glutathione