Sodium selenite-induced oxidative stress and apoptosis in human hepatoma HepG2 cells

Int J Cancer. 1999 May 31;81(5):820-8. doi: 10.1002/(sici)1097-0215(19990531)81:5<820::aid-ijc25>;2-f.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Catalase / pharmacology
  • Deferoxamine / pharmacology
  • Dose-Response Relationship, Drug
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Humans
  • In Situ Nick-End Labeling
  • Intracellular Fluid / drug effects
  • Intracellular Fluid / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Sodium Selenite / pharmacology*
  • Superoxide Dismutase / pharmacology
  • Time Factors
  • Tumor Cells, Cultured


  • Reactive Oxygen Species
  • L-Lactate Dehydrogenase
  • Catalase
  • Superoxide Dismutase
  • Glutathione
  • Sodium Selenite
  • Deferoxamine
  • Glutathione Disulfide