Ebselen induces apoptosis in HepG2 cells through rapid depletion of intracellular thiols

Cheng Feng Yang, Han Ming Shen, Choon Nam Ong

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101 Scopus citations

Abstract

Ebselen, 2-phenyl-1, 2-benzisoselenazol-3(2H)-one, is a synthetic seleno- organic compound with antioxidant capability. In the present study, we systematically examined the ability of ebselen to induce apoptosis in a human hepatoma cell line, HepG2. Ebselen-induced apoptosis was evaluated by (i) TdT-mediated dUTP nick end labeling assay', (ii) analysis of sub-G1 cells; (iii) cell morphology, including cell size and granularity examination; and (iv) DNA gel electrophoresis. The results showed that ebselen was able to induce typical apoptosis in HepG2 cells in a dose- and time-dependent manner. In order to explore the possible mechanisms involved in ebselen- induced apoptosis, the effect of ebselen on intracellular thiol concentrations including reduced glutathione (GSH) and protein thiols and the effect of N-acetylcysteine (NAC) and buthionine sulfoximine (BSO) pretreatment on ebselen-induced apoptosis were investigated. It was found that (i) ebselen rapidly depleted intracellular GSH and protein thiols, moreover, the depletion preceded the occurrence of apoptosis; (ii) NAC, a precursor of intracellular GSH synthesis, significantly alleviated ebselen- induced apoptosis; and (iii) BSO, a specific inhibitor of intracellular GSH synthesis, augmented ebselen-induced apoptosis significantly. Taken together, the present study demonstrates that ebselen is able to induce apoptosis in HepG2 cells, most probably through rapid depletion of intracellular thiols. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)142-152
Number of pages11
JournalArchives of Biochemistry and Biophysics
Volume374
Issue number2
DOIs
StatePublished - Feb 15 2000

Bibliographical note

Funding Information:
The authors would thank Ms. B. L. Ng and Ms. W. Xiong for the excellent technical support in flow cytometry analysis. We also thank Mr. H. Y. Ong and Ms. Y. L. Chew for their technical assistances. Y.C.F. is supported by a Research Scholarship from the National University of Singapore. This research was supported by the National Medical Research Council of Singapore (RP 3970301N).

Keywords

  • Glutathione
  • Protein thiols
  • Redox status
  • Sub-G1 cells
  • TUNEL assay

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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