title: Induction of ER Stress-Mediated Apoptosis by α-Lipoic Acid in A549 Cell Lines.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  α-LA induced ER stress-mediated apoptosis in A549 cells via ROS. α-LA may therefore be clinically useful for treating lung cancer.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Gospel Hospital, Kosin University College of Medicine, Korea.
authors.forename: Jong In
authors.initials: JI
authors.lastname: Kim
authors.forename: Sung-Rae
authors.initials: SR
authors.lastname: Cho
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Eok-Sung
authors.initials: ES
authors.lastname: Park
authors.forename: Ki Nyun
authors.initials: KN
authors.lastname: Kim
authors.forename: Hyung Chul
authors.initials: HC
authors.lastname: Kim
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Lee