title: TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells.
abstract: Overexpression of the cation-permeable channel TRPM8 in prostate cancers might represent a novel opportunity for their treatment. Inhibitors of TRPM8 reduce the growth of prostate cancer cells. We have used two recently described and highly specific blockers, AMTB and JNJ41876666, and RNAi to determine the relevance of TRPM8 expression in the proliferation of non-tumor and tumor cells. Inhibition of the expression or function of the channel reduces proliferation rates and proliferative fraction in all tumor cells tested, but not of non-tumor prostate cells. We observed no consistent acceleration of growth after stimulation of the channel with menthol or icilin, indicating that basal TRPM8 expression is enough to sustain growth of prostate cancer cells.
authors.affiliation: Department of Molecular Biology of Neuronal Signals, Max-Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: María Ll
authors.initials: ML
authors.lastname: Valero
authors.forename: Fernanda
authors.initials: F
authors.lastname: Mello de Queiroz
authors.forename: Walter
authors.initials: W
authors.lastname: Stühmer
authors.forename: Félix
authors.initials: F
authors.lastname: Viana
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pardo
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008610:Menthol / Q000494:pharmacology; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011744:Pyrimidinones / Q000494:pharmacology; D050053:TRPM Cation Channels / Q000235:genetics* / Q000378:metabolism*; D013876:Thiophenes / Q000494:pharmacology; D014162:Transfection; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: D001549:Benzamides; D007473:Ion Channels; C532415:N-(3-aminopropyl)-2-(((3-methylphenyl) methyl)oxy)-N-(2-thienylmethyl)benzamide hydrochloride salt; D011744:Pyrimidinones; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D013876:Thiophenes; D008610:Menthol; C490483:icilin