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 G1 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 G1 arrest, which was rescued by pharmacologic inhibition of these kinases. The action of icilin on G1 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.

• Authors: Su-Hwa Kim, Sung-Young Kim, Eun-Jung Park, Joon Kim, Hyun Ho Park, Insuk So, Seon Jeong Kim, Ju-Hong Jeon
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 406 Issue 1 Pg. 30-5 (Mar 04 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21284938 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Pyrimidinones
• TRPM Cation Channels
• TRPM8 protein, human
• icilin
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 4

Topics

• Cell Line, Tumor
• Enzyme Activation
• G1 Phase (drug effects)
• Humans
• MAP Kinase Kinase 4 (metabolism)
• Male
• Prostatic Neoplasms (metabolism, pathology)
• Pyrimidinones (pharmacology)
• TRPM Cation Channels (agonists)
• p38 Mitogen-Activated Protein Kinases (metabolism)