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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

TRPM8 activation suppresses cellular viability in human melanoma

¹Department of Molecular Morphology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan; ²Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan; and ³Department of Geriatric and Environmental Dermatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

Submitted 19 October 2007 ; accepted in final form 29 May 2008

The transient receptor potential melastatin subfamily (TRPM), which is a mammalian homologue of cell death-regulated genes in Caenorhabditis elegans and Drosophila, has potential roles in the process of the cell cycle and regulation of Ca²⁺ signaling. Among this subfamily, TRPM8 (also known as Trp-p8) is a Ca²⁺-permeable channel that was originally identified as a prostate-specific gene upregulated in tumors. Here we showed that the TRPM8 channel was expressed in human melanoma G-361 cells, and activation of the channel produced sustainable Ca²⁺ influx. The application of menthol, an agonist for TRPM8 channel, elevated cytosolic Ca²⁺ concentration in a concentration-dependent manner with an EC₅₀ value of 286 µM in melanoma cells. Menthol-induced responses were significantly abolished by the removal of external Ca²⁺. Moreover, inward currents at a holding potential of –60 mV in melanoma cells were markedly potentiated by the addition of 300 µM menthol. The most striking finding was that the viability of melanoma cells was dose-dependently depressed in the presence of menthol. These results reveal that a functional TRPM8 protein is expressed in human melanoma cells to involve the mechanism underlying tumor progression via the Ca²⁺ handling pathway, providing us with a novel target of drug development for malignant melanoma.

Ca²⁺-permeable channel; cell viability; G-361; malignant melanoma; menthol; transient receptor potential melastatin

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				A. Slominski Cooling skin cancer: menthol inhibits melanoma growth. Focus on "TRPM8 activation suppresses cellular viability in human melanoma" Am J Physiol Cell Physiol, August 1, 2008; 295(2): C293 - C295. [Full Text] [PDF]