The Role of Waixenicin A as Transient Receptor Potential Melastatin 7 Blocker

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 À 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.

TRPM7 triggers Ca2+ sparks and invadosome formation in neuroblastoma cells

“…We therefore turned our attention to waixenicin-A, a metabolite isolated from extracts of the soft coral S. edmondsoni , which potently and specifically inhibits TRPM7 channels [44,45]. Although it is currently not clear whether this is due to pore blockage or perhaps through other mechanism(s) that involve binding of the compound to TRPM7, waixenicin-A is, to date, considered the most specific inhibitor of this channel.…”

Role of transient receptor potential melastatin type 7 channel in gastric cancer

“…These specific inhibitors did not affect TRPM7-like currents or induce gastric cell death. Therefore, our findings suggested that the TRPM7-specific blockers, NDGA, MK886, AA861, and waixenicin A play an important role in the survival of gastric cancer cells 68, 69. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is one of the most distributed flavonols found in many fruits, vegetables, leaves, and grains 72 .…”

“…Zierler et al 21 suggested that waixenicin A is also a potent inhibitor of TRPM7. In gastric cancer cells, NDGA, AA861, MK886, and waixenicin A all potently blocked TRPM7-like currents and induced cell death, but zileuton did not suppress TRPM7-like current activity or induce cell death 68, 69. To confirm the effects of TRPM7 channel blockers, we also used a pyrazole compound (Pyr3; a specific TRPC3 inhibitor) 70 and 9-phenanthrol (a specific TRPM4 inhibitor) 71 .…”

A NEW CYTOTOXIC DOLABELLANE FROM THE INDONESIAN SOFT CORAL <i>Anthelia</i> sp.

“…On the basis of the above analysis, the planar structure of 1 was established unambiguously. The  7,8 was assigned as E on the basis of NOE correlation between H-17and H-7.The relative stereochemistry of angular methyl (C-15) was established to be the same as that of 2 by extensive NOE analysis in which H-15 correlated with H-20, H-19, and H-10, suggesting angular methyl (H-15), isopropyl group (H-19, H-20), and H-10 to be the same side of 1 (Fig. 2).…”

“…Generally, the activity of those metabolites was reported to show cytotoxic activity against various cell lines [5][6][7]. Moreover, waixenicin A, a xenicanetype compound was identified as a specific inhibitor of TRPM7 ion channels for the treatment of gut motor disorders, gastric and breast cancer [8]. Due to a little chemical information about Anthelia species and its cytotoxicity, we investigated the chemical constituents of an Indonesian Anthelia sp.…”