Brefeldin a induces apoptosis by activating the mitochondrial and death receptor pathways and inhibits focal adhesion kinase-mediated cell invasion

Basic Clin Pharmacol Toxicol. 2013 Nov;113(5):329-38. doi: 10.1111/bcpt.12107. Epub 2013 Jul 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • BH3 Interacting Domain Death Agonist Protein / genetics
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Brefeldin A / pharmacology*
  • Carcinoma, Ovarian Epithelial
  • Caspase 8 / genetics
  • Caspase 8 / 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*
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Humans
  • Membrane Potential, Mitochondrial
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms
  • Reactive Oxygen Species / metabolism

Substances

  • 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