Sodium selenite-induced oxidative stress and apoptosis in human hepatoma HepG2 cells.
The mechanisms involved in the anti-carcinogenic activity of selenium remain to be elucidated. In the present study, we examined sodium selenite-induced oxidative stress and apoptosis in a human hepatoma cell line (HepG2). Sodium selenite (10 microM) exerted clear cytotoxic effect, as shown by the significant increase of lactate dehydrogenase leakage. Selenite-induced DNA alterations in apoptosis were studied by: 1. comet assay; 2. TdT-mediated dUTP nick end-labeling assay. In addition, characteristic apoptotic morphological alterations were also observed in selenite-treated cells. Our results clearly show that Se-induced cell death occurs predominantly in the form of apoptosis. Selenite-induced oxidative stress was evaluated by the measurement of reactive oxygen species production using lucigenin-dependent chemiluminescence. The involvement of glutathione in selenite-induced oxidative stress was further demonstrated by the concurrent decline of intracellular reduced glutathione and increase of oxidized glutathione contents in Se-treated cells. Moreover, the finding that selenite-induced oxidative stress and apoptosis was significantly attenuated by superoxide dismutase, catalase and deferoxamine provides additional evidence to suggest that Se-induced oxidative stress mediates the induction of apoptosis, a mechanism related to the anti-carcinogenic and chemopreventive effect of Se.
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured