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 (86Rb(+)) efflux and proliferation assays. 1-EBIO and riluzole evoked concentration-dependent increases in 86Rb(+) efflux from LNCaP and PC-3 cells that were sensitive to inhibition by intermediate-conductance Ca(2+)-activated K(+) channel (IK(Ca)) blockers clotrimazole and charybdotoxin. Blockers of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, iberiotoxin, or small-conductance Ca(2+)-activated K(+) (SK(Ca)) 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 riluzole-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), BK(Ca) channel openers had no effect on LNCaP and PC-3 proliferation. These results demonstrate that IK(Ca) channels play an important role in the regulation of human prostate cancer cell proliferation.
Parihar
Ashutosh S
AS
Neuroscience Research, Global Pharmaceutical Research and Development, Department R4PM, Building AP9A, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6125, USA.
Coghlan
Michael J
MJ
Gopalakrishnan
Murali
M
Shieh
Char-Chang
CC
D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D002120:Calcium Channel Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use
D001562:Benzimidazoles; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D019782:Riluzole; C102635:1-ethyl-2-benzimidazolinone