Korean J Thorac Cardiovasc Surg.  2012 Feb;45(1):1-10.

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

• Kim JI
• Cho SR
• Lee CM
• Park ES
• Kim KN
• Kim HC
• Lee HY

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.

Keyword

Lung neoplasms; Cell death; Neoplasm marker

MeSH Terms

Acetylcysteine
Apoptosis
Blotting, Western
Cell Death
Cell Line
DNA Fragmentation
Endoplasmic Reticulum
Flow Cytometry
Lung Neoplasms
Obesity
Reactive Oxygen Species
Thioctic Acid
X-Linked Inhibitor of Apoptosis Protein
Acetylcysteine
Reactive Oxygen Species
Thioctic Acid
X-Linked Inhibitor of Apoptosis Protein