Dual role of glutathione in selenite-induced oxidative stress and apoptosis in human hepatoma cells

Han Ming Shen, Cheng Feng Yang, Jin Liu, Choon Nam Ong

Research output: Contribution to journalArticlepeer-review

113 Citations (SciVal)


It is well known that glutathione, the major intracellular antioxidant, is closely involved in the metabolism and bioactivity of selenium. In the present study, glutathione was demonstrated to play a dual role on selenite (Se)-induced oxidative stress and apoptosis in human hepatoma HepG2 cells. The experiment was carried out in two different modes to modulate intracellular reduced glutathione (GSH) content. In Mode A (pretreatment), cells were pretreated with N-acetylcysteine (NAC), buthionine sulfoximine (BSO), or GSH prior to Se exposure. In Mode B (simultaneous treatment), cells were treated with Se and NAC, BSO, or GSH simultaneously. It was found that Se-induced oxidative stress and apoptosis are closely related to the intracellular level of GSH. Both the increase and depletion of GSH content significantly enhanced Se-induced oxidative stress and apoptosis in HepG2 cells. Results from this study clearly demonstrated that GSH has a dual role in the effects of Se on cancer cells: (i) GSH acts as a pro-oxidant, facilitating Se-induced oxidative stress, and (ii) GSH acts as an antioxidant, protecting against Se-induced oxidative stress and apoptosis. Understanding such a unique association between GSH and Se may help to explain the controversy in the literature over the complex relationship between selenium and glutathione, and ultimately the capability of selenium to prevent cancer.

Original languageEnglish
Pages (from-to)1115-1124
Number of pages10
JournalFree Radical Biology and Medicine
Issue number7
StatePublished - Apr 2000

Bibliographical note

Funding Information:
This study was supported by Singapore National Medical Research Council (Grant RP3970301N) and the Singapore Cancer Society. We would like to thank Mr. Ong H.Y. and Ms. Ng Bee Ling for their technical support, and Dr. G.N. Wogan for his valuable comments. Y.C.F. and L.J. are supported by the National University of Singapore Research Scholarships.


  • Apoptosis
  • Cancer
  • Free radicals
  • Glutathione
  • Oxidative stress
  • Selenite
  • Selenium

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


Dive into the research topics of 'Dual role of glutathione in selenite-induced oxidative stress and apoptosis in human hepatoma cells'. Together they form a unique fingerprint.

Cite this