KMID : 0364020120450010001
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Korean Journal of Thoracic and Cardiovascular Surgery 2012 Volume.45 No. 1 p.1 ~ p.10
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Induction of ER Stress-Mediated Apoptosis by ?-Lipoic Acid in A549 Cell Lines
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Kim Jong-In
Cho Sung-Rae Lee Chang-Min Park Eok-Sung Kim Ki-Nyun Kim Hyung-Chul Lee Hae-Young
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Abstract
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Background: ?-Lipoic acid (?-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 ?-LA in a lung cancer cell line, A549.
Materials and Methods: ?-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: ?-LA induced apoptosis and DNA fragmentation in A549 cells in a dose- and time-dependent manner. ?-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 ?-LA, and the antioxidant N-acetyl-L-cysteine decreased the ?-LA-induced increase in expression of apoptosis and ER stress-related proteins.
Conclusion: ?-LA induced ER stress-mediated apoptosis in A549 cells via ROS. ?-LA may therefore be clinically useful for treating lung cancer.
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KEYWORD
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Lung neoplasms, Cell death, Neoplasm marker
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