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: Seon A Lee, Yun J Kim, Chung S Lee
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 113 Issue 5 Pg. 329-38 (Nov 2013) ISSN: 1742-7843 [Electronic] England
• PMID: 23826964 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Chemical References

• BH3 Interacting Domain Death Agonist Protein
• BID protein, human
• Reactive Oxygen Species
• Brefeldin A
• Cytochromes c
• Focal Adhesion Protein-Tyrosine Kinases
• CASP8 protein, human
• Caspase 8

Topics

• Apoptosis (drug effects)
• BH3 Interacting Domain Death Agonist Protein (genetics, metabolism)
• Brefeldin A (pharmacology)
• Carcinoma, Ovarian Epithelial
• Caspase 8 (genetics, metabolism)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• DNA Damage (drug effects)
• DNA Fragmentation (drug effects)
• Focal Adhesion Protein-Tyrosine Kinases (antagonists & inhibitors, genetics, metabolism)
• Humans
• Membrane Potential, Mitochondrial
• Mitochondria (drug effects, metabolism)
• Neoplasms, Glandular and Epithelial
• Ovarian Neoplasms
• Reactive Oxygen Species (metabolism)