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Updated: Jul 4, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
TRPM8 activation suppresses cellular viability in human melanoma
Hisao Yamamura1, Shinya Ugawa, Takashi Ueda
1Dept. of Molecular Morphology, Graduate School of Medical Sciences, Nagoya City Univ., 1 Kawasumi Mizuhocho Mizuhoku, Nagoya 467-8601, Japan. yamamura@med.nagoya-cu.ac.jp
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(2+) signaling. Among this subfamily, TRPM8 (also known as Trp-p8) is a Ca(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(2+) influx. The application of menthol, an agonist for TRPM8 channel, elevated cytosolic Ca(2+) concentration in a concentration-dependent manner with an EC(50) value of 286 microM in melanoma cells. Menthol-induced responses were significantly abolished by the removal of external Ca(2+). Moreover, inward currents at a holding potential of -60 mV in melanoma cells were markedly potentiated by the addition of 300 microM 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(2+) handling pathway, providing us with a novel target of drug development for malignant melanoma.
Insights
The transient receptor potential melastatin 8 (TRPM8) channel is present in human melanoma cells. Menthol activates TRPM8, increasing calcium influx and decreasing melanoma cell viability, suggesting TRPM8 as a drug target.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- The transient receptor potential melastatin subfamily (TRPM) plays roles in cell cycle and calcium (Ca2+) signaling.
- TRPM8, a Ca2+-permeable channel, is upregulated in tumors and identified as Trp-p8.
- TRPM8 is implicated in cell death regulation.
Purpose of the Study:
- To investigate the expression and function of TRPM8 in human melanoma cells.
- To determine the effect of TRPM8 activation on calcium signaling and cell viability in melanoma.
- To explore TRPM8 as a potential therapeutic target for malignant melanoma.
Main Methods:
- Expression analysis of TRPM8 in human melanoma G-361 cells.
- Measurement of cytosolic Ca2+ concentration using menthol as a TRPM8 agonist.
- Electrophysiological recordings to assess TRPM8 channel activity.
- Cell viability assays in the presence of menthol.
Main Results:
- TRPM8 channel expression was confirmed in human melanoma G-361 cells.
- Menthol, a TRPM8 agonist, induced concentration-dependent Ca2+ influx, dependent on external Ca2+.
- Menthol application potentiated inward currents and significantly reduced melanoma cell viability.
- An EC50 value of 286 microM was determined for menthol-induced Ca2+ elevation.
Conclusions:
- Functional TRPM8 protein is expressed in human melanoma cells.
- TRPM8 activation influences Ca2+ handling pathways involved in melanoma progression.
- TRPM8 represents a novel drug development target for malignant melanoma treatment.
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