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

Abstract

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.

• Authors: Ashutosh S Parihar, Michael J Coghlan, Murali Gopalakrishnan, Char-Chang Shieh
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 471 Issue 3 Pg. 157-64 (Jun 27 2003) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12826234 (Publication Type: Journal Article)

Chemical References

• Benzimidazoles
• Calcium Channel Agonists
• Calcium Channel Blockers
• Potassium Channels, Calcium-Activated
• Riluzole
• 1-ethyl-2-benzimidazolinone

Topics

• Benzimidazoles (pharmacology, therapeutic use)
• Calcium Channel Agonists (pharmacology, therapeutic use)
• Calcium Channel Blockers (pharmacology, therapeutic use)
• Cell Division (drug effects, physiology)
• Cell Line, Tumor (cytology, drug effects, physiology)
• Dose-Response Relationship, Drug
• Humans
• Male
• Potassium Channels, Calcium-Activated (agonists, antagonists & inhibitors, physiology)
• Prostatic Neoplasms (drug therapy, pathology)
• Riluzole (pharmacology, therapeutic use)