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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzamides / pharmacology
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Cell Cycle / drug effects
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Cell Cycle / genetics
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Cell Line
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Humans
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Ion Channels / genetics*
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Ion Channels / metabolism*
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Male
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Menthol / pharmacology
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Prostate / cytology
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Prostate / metabolism
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Prostatic Neoplasms / genetics*
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / pathology
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Pyrimidinones / pharmacology
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TRPM Cation Channels / genetics*
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TRPM Cation Channels / metabolism*
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Thiophenes / pharmacology
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Transfection
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Wound Healing / drug effects
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Wound Healing / genetics
Substances
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Benzamides
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Ion Channels
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N-(3-aminopropyl)-2-(((3-methylphenyl) methyl)oxy)-N-(2-thienylmethyl)benzamide hydrochloride salt
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Pyrimidinones
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TRPM Cation Channels
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TRPM8 protein, human
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Thiophenes
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Menthol
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icilin
Grants and funding
Financed by the Max-Planck Society and grants SAF2010-14990 and PROMETEO2010-046 to FV. MV was the recipient of a predoctoral fellowship of the Spanish Government (F.P.I). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.