Icilin induces G1 arrest through activating JNK and p38 kinase in a TRPM8-independent manner

Abstract

Aberrant regulation of cell cycle confers a limitless replicative potential, which is a hallmark of cancer. Currently, the compounds targeting the cell cycle are undergoing cancer clinical trials. In this study, we demonstrated that icilin, a cooling compound, induces Cl arrest in PC-3 prostate cancer cells without cell death. Icilin modulated the expression level of various cell cycle regulators at transcription or post-translational levels. In addition, icilin activated JNK and p38 kinase pathways, but not ERK. Both JNK and p38 kinases cooperatively mediated icilin-induced Cl arrest, which was rescued by pharmacologic inhibition of these kinases. The action of icilin on Cl arrest was unrelated to the activation of TRPM8 calcium channel. Our findings suggest that icilin is a valuable chemical probe for future investigation aiming at delineating the molecular mechanisms of cell cycle regulation in prostate cancer. (C) 2011 Elsevier Inc. All rights reserved.