Involvement of K(+)-Cl(-)-cotransport in the apoptosis induced by N-ethylmaleimide in HepG2 human hepatoblastoma cells

Eur J Pharmacol. 2001 Apr 20;418(1-2):1-5. doi: 10.1016/s0014-2999(01)00861-5.


The role of K(+)-Cl(-)-cotransport in apoptosis in human cancer cells was investigated. N-Ethylmaleimide, a K(+)-Cl(-)-cotransport activator, induced apoptosis in a dose-dependent manner in HepG2 human hepatoblastoma cells. N-Ethylmaleimide induced Cl(-)-dependent K(+) efflux, indicating that K(+)-Cl(-)-cotransport is functionally present in HepG2 cells. Calyculin-A and genistein, inhibitors of K(+)-Cl(-)-cotransport, significantly prevented both K(+)-Cl(-)-cotransport activation and apoptosis induced by N-ethylmaleimide. These results demonstrate, for the first time, a novel role for K(+)-Cl(-)-cotransport in apoptosis in human hepatoma cells. These results further suggest that K(+)-Cl(-)-cotransport may be a valuable target for therapeutic interventions for human hepatoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carrier Proteins / metabolism*
  • Chlorides / metabolism
  • Ethylmaleimide / pharmacology*
  • Flow Cytometry
  • Genistein / pharmacology
  • Humans
  • Ion Transport / drug effects
  • Marine Toxins
  • Oxazoles / pharmacology
  • Potassium / metabolism
  • Symporters*
  • Tumor Cells, Cultured


  • Carrier Proteins
  • Chlorides
  • Marine Toxins
  • Oxazoles
  • Symporters
  • potassium-chloride symporters
  • calyculin A
  • Genistein
  • Ethylmaleimide
  • Potassium