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

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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