Inhibition of cell growth by K+ channel modulators is due to interference with agonist-induced Ca2+ release.
The effects of K+ channel modulators, tetraethylammonium, 4-aminopyridine and diazoxide, and high extracellular K+ on cell growth and agonist-induced intracellular Ca2+ mobilization were investigated. Two human brain tumour cell lines, U-373 MG astrocytoma and SK-N-MC neuroblastoma, were used as model cellular systems. K+ channel modulators and increased extracellular K+ concentration inhibited tumour cell growth in a dose-related fashion in both cell lines. In addition, agonist (carbachol or serum)-induced intracellular Ca2+ mobilization was also blocked by the pretreatment of growth-inhibitory concentrations of K+ channel modulators and high extracellular K+. Thus, these results suggest that K+ channel modulators are effective inhibitors of brain tumour cell growth and that their growth regulation may be due to the interference with the intracellular Ca2+ signalling mechanisms.
Lee
Y S
YS
Department of Neurological Surgery, Loyola University Medical Center, Maywood, IL 60153.
Sayeed
M M
MM
Wurster
R D
RD
D015761:4-Aminopyridine / Q000494:pharmacology; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects*; D015398:Signal Transduction; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015221:Potassium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D003981:Diazoxide; D002118:Calcium