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
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis*
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Carcinoma, Hepatocellular / enzymology
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Caspases / analysis
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Caspases / metabolism
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Cell Line, Tumor
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Enzyme Activation
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Free Radical Scavengers / pharmacology*
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Humans
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Liver Neoplasms / enzymology
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PTEN Phosphohydrolase / metabolism*
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism*
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Reactive Oxygen Species / analysis
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Reactive Oxygen Species / antagonists & inhibitors*
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Thioctic Acid / pharmacology*
Substances
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Antineoplastic Agents
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Free Radical Scavengers
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Reactive Oxygen Species
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Thioctic Acid
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Proto-Oncogene Proteins c-akt
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PTEN Phosphohydrolase
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PTEN protein, human
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Caspases