Effects of intermediate-conductance Ca2+ activated K+-channel modulators on human prostate cancer cell proliferation

The effects of 1-ethyl-2-benzimidazolinone (1-EBIO) and riluzole on human prostate cancer cells, LNCaP and PC-3, were evaluated using rubidium (Rb-86(+)) efflux and proliferation assays. 1-EBIO and riluzole evoked concentration-dependent increases in Rb-86(+) efflux from LNCaP and PC-3 cells that were sensitive to inhibition by intermediate-conductance Ca2+-activated K+ channel (IKCa) blockers clotrimazole and charybdotoxin. Blockers of large-conductance Ca2+-activated K+ (IKCa) channel, iberiotoxin, or small-conductance Ca2+-activated K+ (SKCa) channel, apamin or scyllatoxin, had no effect. Concurrently, both 1-EBIO and riluzole evoked concentration-dependent increases in proliferation from human prostate cancer cell lines (LNCaP and PC-3 cells). Clotrimazole and charybdotoxin, but not iberiotoxin, apamin or scyllatoxin, inhibited 1-EBIO- and ffluzole-evoked increases in proliferation from LNCaP and PC-3 cells. N-(3-(trifluoromethyl)phenyl)-N'-(2-hydroxy-5-chlorophenyl)urea (NS-1608) and 2-amino-5-(2-fluorophenyl)-4-methyl-1H-pyrrole-3-carbonitrile (NS-8), BKCa channel openers had no effect on LNCaP and PC-3 proliferation. These results demonstrate that IKCa channels play an important role in the regulation of human prostate cancer cell proliferation. (C) 2003 Elsevier Science B.V. All rights reserved.