title: 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.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Su-Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Park
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Seon Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
mesh_terms: D045744:Cell Line, Tumor; D004789:Enzyme Activation; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011744:Pyrimidinones / Q000494:pharmacology*; D050053:TRPM Cation Channels / Q000819:agonists*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D011744:Pyrimidinones; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; C490483:icilin; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4