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http://dx.doi.org/10.5090/kjtcs.2012.45.1.1

Induction of ER Stress-Mediated Apoptosis by ${\alpha}$-Lipoic Acid in A549 Cell Lines  

Kim, Jong-In (Department of Thoracic and Cardiovascular Surgery, Gospel Hospital, Kosin University College of Medicine)
Cho, Sung-Rae (Department of Thoracic and Cardiovascular Surgery, Gospel Hospital, Kosin University College of Medicine)
Lee, Chang-Min (Department of Thoracic and Cardiovascular Surgery, Gospel Hospital, Kosin University College of Medicine)
Park, Eok-Sung (Department of Thoracic and Cardiovascular Surgery, Gospel Hospital, Kosin University College of Medicine)
Kim, Ki-Nyun (Department of Thoracic and Cardiovascular Surgery, Gospel Hospital, Kosin University College of Medicine)
Kim, Hyung-Chul (Department of Thoracic and Cardiovascular Surgery, Gospel Hospital, Kosin University College of Medicine)
Lee, Hae-Young (Department of Thoracic and Cardiovascular Surgery, Gospel Hospital, Kosin University College of Medicine)
Publication Information
Journal of Chest Surgery / v.45, no.1, 2012 , pp. 1-10 More about this Journal
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.
Keywords
Lung neoplasms; Cell death; Neoplasm marker;
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