1. TRPM8 activation suppresses cellular viability in human melanoma
- Author
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Yamamura, Hisao, Ugawa, Shinya, Ueda, Takashi, Morita, Akimichi, and Shimada, Shoichi
- Subjects
Calcium channels -- Properties ,Biological transport, Active -- Evaluation ,Melanoma -- Development and progression ,Cell physiology -- Research ,Biological sciences - Abstract
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 [Ca.sup.2+] signaling. Among this subfamily, TRPM8 (also known as Trp-p8) is a [Ca.sup.2+]-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 [Ca.sup.2+] influx. The application of menthol, an agonist for TRPM8 channel, elevated cytosolic [Ca.sup.2+] concentration in a concentration-dependent manner with an E[C.sub.50] value of 286 [micro]M in melanoma cells. Menthol-induced responses were significantly abolished by the removal of external [Ca.sup.2+]. Moreover, inward currents at a holding potential of -60 mV in melanoma cells were markedly potentiated by the addition of 300 [micro]M 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 [Ca.sup.2+] handling pathway, providing us with a novel target of drug development for malignant melanoma. [Ca.sup.2+]-permeable channel; cell viability; G-361; malignant melanoma; menthol; transient receptor potential melastatin
- Published
- 2008