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The role of transient receptor potential channel blockers in human gastric cancer cell viability

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Transient receptor potential cation channel, subfamily M, receptor 7 (TRPM7) is a ubiquitous divalent-selective ion channel with its own kinase domain. Human gastric cancer cells express the TRPM7 channel, and the presence of this channel is essential for cell survival. Recent studies have suggested that 5-lipoxygenase (5-LOX) inhibitors are potent blockers of the TRPM7 channels. The aim of this study was to show the effects of 5-LOX inhibitors on the growth and survival of gastric cancer cells. Among 5-LOX inhibitors, nordihydroguaiaretic acid (NDGA), 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861), and 3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-tert-butylthioindol-2-yl]-2,2-dimethylpropanoic acid (MK886) were potent blockers of TRPM7-like currents in gastric cancer cells and also induced cell death. However, zileuton was ineffective in suppressing TRPM7-like current activity and inducing cell death. Moreover, a specific transient receptor potential cation channel, subfamily C, member 3 (TRPC3) inhibitor, a pyrazole compound (Pyr3), and a specific melastatin TRP (TRPM4) inhibitor, 9-phenanthrol, did not affect TRPM7-like currents or induce cell death. We conclude that TRPM7 has an important role in the growth and survival of gastric cancer cells and a likely potential target for the pharmacological treatment of gastric cancer.
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Keywords: 5-lipoxygenase inhibitors; 9-phenanthrol; 9-phénanthrol; Pyr3; TRPM7; cellule cancéreuse gastrique; gastric cancer cell; inhibiteurs de la 5-lipoxygénase

Document Type: Research Article

Affiliations: 1: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea. 2: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. 3: Department of Biomedical Informatics, University of Utah, Salt Lake City, UT 84112, USA. 4: Division of Gastroenterology, University of TSUKUBA Graduate School for Comprehensive Human Sciences, Japan. 5: Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University, Seoul 133-791, Republic of Korea.

Publication date: February 20, 2012

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