Induction of ER Stress-Mediated Apoptosis by alpha-Lipoic Acid in A549 Cell Lines

ABSTRACT

BACKGROUND: alpha-Lipoic acid (alpha-LA) has been studied as an anticancer agent as well as a therapeutic agent for diabetes and obesity. We performed this study to evaluate the anticancer effects and mechanisms of alpha-LA in a lung cancer cell line, A549. MATERIALS AND METHODS: alpha-LA-induced apoptosis of A549 cells was detected by fluorescence-activated cell sorting analysis and a DNA fragmentation assay. Expression of apoptosis-related genes was analyzed by western blot and reverse transcription-polymerase chain reaction analyses. RESULTS: alpha-LA induced apoptosis and DNA fragmentation in A549 cells in a dose- and time-dependent manner. alpha-LA increased caspase activity and the degradation of poly (ADP-ribose) polymerase. It induced expression of endoplasmic reticulum (ER) stress-related genes, such as glucose-regulated protein 78, C/EBP-homologous protein, and the short form of X-box binding protein-1, and decreased expression of the anti-apoptotic protein, X-linked inhibitor of apoptosis protein. Reactive oxygen species (ROS) production was induced by alpha-LA, and the antioxidant N-acetyl-L-cysteine decreased the alpha-LA-induced increase in expression of apoptosis and ER stress-related proteins. CONCLUSION: alpha-LA induced ER stress-mediated apoptosis in A549 cells via ROS. alpha-LA may therefore be clinically useful for treating lung cancer.