Abstract
Menthol, a naturally occurring compound from peppermint oil, binds and activates the TRPM8 Ca 2+-permeable channel that exhibits abnormal expression patterns in prostate cancer, suggesting that TRPM8 links Ca 2+ transport pathways to tumor biology. We thus investigated the cellular responses of prostate cancer cells to menthol. Here we found that menthol increases [Ca 2+] i via Ca 2+ influx mechanism(s) independent of TRPM8 in PC-3 cells. We demonstrated that menthol induces cell death at supramillimolar concentrations in PC-3 cells and the cell death is not suppressed by low extracellular Ca 2+ condition which indicates that menthol-induced cell death is not associated with Ca 2+ influx pathways. In addition, we showed that menthol increases a phosphorylated form of c-jun N-terminal kinase (JNK) in PC-3 cells through TRPM8-independent mechanisms. Thus, our data indicate that there is an apparent lack of causality between TRPM8 activation and menthol-induced cell death and that menthol can regulate TRPM8-independent Ca 2+-transport and cellular processes.
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Schedule a callMore From: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
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