Involvement of K(+)-Cl(-)-cotransport in the apoptosis induced by N-ethylmaleimide in HepG2 human hepatoblastoma cells.
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.
Kim
J A
JA
College of Pharmacy, Yeungnam University, Kyongsan 712-749, South Korea.
Kang
Y S
YS
Lee
Y S
YS
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology*; D005434:Flow Cytometry; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D027981:Symporters; D014407:Tumor Cells, Cultured; D000096922:K Cl- Cotransporters
D002352:Carrier Proteins; D002712:Chlorides; D005033:Ethylmaleimide; D019833:Genistein; D008387:Marine Toxins; D010080:Oxazoles; D011188:Potassium; D027981:Symporters; D000096922:K Cl- Cotransporters; C059041:calyculin A