The role of waixenicin A as transient receptor potential melastatin 7 blocker.
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.
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Korea.
Byung J
BJ
Kim
Joo H
JH
Nam
Young K
YK
Kwon
Insuk
I
So
Seon J
SJ
Kim
D000085:Acetates / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D017346:Protein Serine-Threonine Kinases; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D050053:TRPM Cation Channels / Q000378:metabolism*
D000085:Acetates; D004224:Diterpenes; D050053:TRPM Cation Channels; C568854:waixenicin A; C421903:Trpm7 protein, mouse; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human