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

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Date 2012 Feb 25
PMID 22363901
Citations 6
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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.

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.

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References
1.
Yamaguchi H, Wang H . CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem. 2004; 279(44):45495-502. DOI: 10.1074/jbc.M406933200. View

2.
Forsberg L, de Faire U, Morgenstern R . Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys. 2001; 389(1):84-93. DOI: 10.1006/abbi.2001.2295. View

3.
Gaut J, Hendershot L . The modification and assembly of proteins in the endoplasmic reticulum. Curr Opin Cell Biol. 1993; 5(4):589-95. DOI: 10.1016/0955-0674(93)90127-c. View

4.
Kuo P, Chiang L, Lin C . Resveratrol- induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells. Life Sci. 2002; 72(1):23-34. DOI: 10.1016/s0024-3205(02)02177-x. View

5.
Pierce R, Campbell J, STEPHENSON A, Franklin C, Chaisson M, Poot M . Disruption of redox homeostasis in tumor necrosis factor-induced apoptosis in a murine hepatocyte cell line. Am J Pathol. 2000; 157(1):221-36. PMC: 1850198. DOI: 10.1016/S0002-9440(10)64533-6. View