Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway

FEBS Lett. 2008 May 28;582(12):1667-71. doi: 10.1016/j.febslet.2008.04.021. Epub 2008 Apr 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Carcinoma, Hepatocellular / enzymology
  • Caspases / analysis
  • Caspases / metabolism
  • Cell Line, Tumor
  • Enzyme Activation
  • Free Radical Scavengers / pharmacology*
  • Humans
  • Liver Neoplasms / enzymology
  • PTEN Phosphohydrolase / metabolism*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reactive Oxygen Species / analysis
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Thioctic Acid / pharmacology*

Substances

  • Antineoplastic Agents
  • Free Radical Scavengers
  • Reactive Oxygen Species
  • Thioctic Acid
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Caspases