Role of reactive oxygen species in apoptosis induced by N-ethylmaleimide in HepG2 human hepatoblastoma cells

Eur J Pharmacol. 2001 Dec 14;433(1):1-6. doi: 10.1016/s0014-2999(01)01420-0.


We have previously reported that N-ethylmaleimide induces apoptosis through activation of K(+), Cl(-)-cotransport in HepG2 human hepatoblastoma cells. In this study, we investigated the role for reactive oxygen species as a mediator of the apoptosis induced by N-ethylmaleimide. N-ethylmaleimide induced a significant elevation of intracellular level of reactive oxygen species. Treatment with antioxidants (N-acetyl cysteine, N,N'-diphenyl-p-phenylenediamine) which markedly suppressed generation of reactive oxygen species, significantly inhibited the N-ethylmaleimide-induced activation of K(+), Cl(-)-cotransport and apoptosis. Inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, D-(+)-neopterine) also significantly blunted the generation of reactive oxygen species, activation of K(+), Cl(-)-cotransport and apoptosis induced by N-ethylmaleimide. These results suggest that reactive oxygen species generated through activation of NADPH oxidase may play a role in the N-ethylmaleimide-induced stimulation of K(+), Cl(-)-cotransport and apoptosis in HepG2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Chlorides / metabolism
  • Ethylmaleimide / pharmacology*
  • Hepatoblastoma / metabolism
  • Hepatoblastoma / pathology*
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • NADPH Oxidases / physiology
  • Potassium / metabolism
  • Reactive Oxygen Species*
  • Symporters / physiology


  • Chlorides
  • Reactive Oxygen Species
  • Symporters
  • potassium-chloride symporters
  • NADPH Oxidases
  • Ethylmaleimide
  • Potassium