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Brefeldin A Induces Apoptosis by Activating the Mitochondrial and Death Receptor Pathways and Inhibits Focal Adhesion Kinase‐Mediated Cell Invasion
Author(s) -
Lee Seon A.,
Kim Yun J.,
Lee Chung S.
Publication year - 2013
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12107
Subject(s) - brefeldin a , microbiology and biotechnology , focal adhesion , apoptosis , programmed cell death , cell adhesion , chemistry , cancer cell , caspase , biology , cell , signal transduction , golgi apparatus , cancer , biochemistry , genetics , endoplasmic reticulum
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 B id‐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.