title: Brefeldin a induces apoptosis by activating the mitochondrial and death receptor pathways and inhibits focal adhesion kinase-mediated cell invasion.
abstract: Brefeldin A induces apoptosis in various cancer cells; however, the apoptotic process in cancer cells exposed to brefeldin A remains unclear. In addition, it is unclear whether brefeldin A-induced apoptosis is mediated by the formation of reactive oxygen species. Furthermore, the effect of brefeldin A on the invasion and migration of human epithelial ovarian cancer cells has not been studied. Therefore, we investigated the effect of brefeldin A on apoptosis, cell adhesion and migration using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. The results suggest that brefeldin A 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 brefeldin A seems to be mediated by formation of reactive oxygen species and depletion of GSH, which results in the activation of apoptotic caspases. Brefeldin A inhibited foetal bovine serum-induced adhesion and migration of OVCAR-3 cells. Brefeldin A may prevent the foetal bovine serum-induced cell adhesion and migration by limiting the focal adhesion kinase-dependent activation of cytoskeletal-associated components.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
authors.forename: Seon A
authors.initials: SA
authors.lastname: Lee
authors.forename: Yun J
authors.initials: YJ
authors.lastname: Kim
authors.forename: Chung S
authors.initials: CS
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism; D020126:Brefeldin A / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial; D010051:Ovarian Neoplasms; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D017382:Reactive Oxygen Species; D020126:Brefeldin A; D045304:Cytochromes c; D051416:Focal Adhesion Protein-Tyrosine Kinases; C505530:CASP8 protein, human; D053181:Caspase 8