Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway.
We report here that alpha-lipoic acid (alpha-LA), a naturally-occurring antioxidant, scavenges reactive oxygen species (ROS) followed by an increase in apoptosis of human hepatoma cells. Apoptosis induced by alpha-LA was dependent upon the activation of the caspase cascade and the mitochondrial death pathway. alpha-LA induced increases in caspase-9 and caspase-3 but had no significant effect on caspase-8 activity. Apoptosis induced by alpha-LA was found to be mediated through the tensin homologue deleted on chromosome 10 (PTEN)/Akt pathway. Prior to cell apoptosis, PTEN was activated and its downstream target Akt was inhibited. Our findings indicate that increasing ROS scavenging could be a therapeutic strategy to treat cancer.
Shi
Dong-Yun
DY
Department of Biochemistry, Shanghai Medical College of Fudan University, Free Radical Research Center of Fudan University, Shanghai 200032, PR China. cyshi@fudan.edu.cn
Liu
Hong-Lei
HL
Stern
Jeremy S
JS
Yu
Pei-Zhong
PZ
Liu
Shan-Lin
SL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000037:antagonists & inhibitors*; D008063:Thioctic Acid / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020169:Caspases