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

• Published in: Journal of chest surgery 2012, 45(1), , pp.1-10
• Main Authors: 김종인, 조성래, 이창민, 박억숭, 김기년, 김형철, 이해영
• Format: Article
• Language: English
• Subjects: 흉부외과학
• ISSN: 2765-1606; 2765-1614

Background: α-Lipoic acid (α-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 α-LA in a lung cancer cell line, A549. Materials and Methods: α-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: α-LA induced apoptosis and DNA fragmentation in A549 cells in a dose- and time-dependent manner. α-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 α-LA, and the antioxidant N-acetyl-L-cysteine decreased the α-LA-induced increase in expression of apoptosis and ER stress-related proteins. Conclusion: α-LA induced ER stress-mediated apoptosis in A549 cells via ROS. α-LA may therefore be clinically useful for treating lung cancer. KCI Citation Count: 1