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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)
  • Received : 2010.09.30
  • Accepted : 2011.11.25
  • Published : 2012.02.05

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

References

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