The role of waixenicin A as transient receptor potential melastatin 7 blocker

Basic Clin Pharmacol Toxicol. 2013 Feb;112(2):83-9. doi: 10.1111/j.1742-7843.2012.00929.x. Epub 2012 Sep 25.

Abstract

Transient receptor potential melastatin 7 (TRPM7) plays a role in a number of physiological and pharmacological functions in variety of cells. The aim of this study was to clarify the role for TRPM7 channels and the effect of waixenicin A on the pacemaking activity of interstitial cells of Cajal (ICCs) and on the cell viability of the human gastric and breast adenocarcinoma cell lines, AGS and MCF-7, respectively. Waixenicin A decreased the amplitude of pacemaker potentials in cultured ICC clusters and inhibited TRPM7 currents, but had no effect on Ca(2+) -activated Cl(-) conductance (ANO1). Furthermore, waixenicin A was found to inhibit the growth and survival of AGS and MCF-7 cells. These findings indicate that TRPM7 channel modulates intestinal motility and regulates the pathophysiology of human gastric and breast adenocarcinoma cells. These findings suggest that TRPM7 channel be considered a potential target for the treatment of gut motor disorders and gastric and breast cancer.

MeSH terms

  • Acetates / pharmacology*
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Animals
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival
  • Diterpenes / pharmacology*
  • Female
  • Gastrointestinal Motility / drug effects
  • Humans
  • Interstitial Cells of Cajal / drug effects*
  • Interstitial Cells of Cajal / metabolism
  • Male
  • Membrane Potentials / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Protein Serine-Threonine Kinases
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / pathology
  • TRPM Cation Channels / metabolism*

Substances

  • Acetates
  • Diterpenes
  • TRPM Cation Channels
  • waixenicin A
  • Trpm7 protein, mouse
  • Protein Serine-Threonine Kinases
  • TRPM7 protein, human