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.