Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
Can J Physiol Pharmacol. 2012 Feb;90(2):175-86. doi: 10.1139/y11-114. Epub 2012 Feb 6.
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.
瞬时受体电位阳离子通道亚家族 M，受体 7（TRPM7）是一种普遍存在的二价选择性离子通道，具有自己的激酶结构域。人类胃癌细胞表达 TRPM7 通道，该通道的存在对于细胞存活至关重要。最近的研究表明，5-脂氧合酶（5-LOX）抑制剂是 TRPM7 通道的有效阻断剂。本研究旨在探讨 5-LOX 抑制剂对胃癌细胞生长和存活的影响。在 5-LOX 抑制剂中，壬二酸（NDGA）、2,3,5-三甲基-6-（12-羟基-5,10-十二碳二炔基）-1,4-苯醌（AA861）和 3-[1-（对氯苄基）-5-（异丙基）-3-叔丁基硫代吲哚-2-基]-2,2-二甲基丙 酸（MK886）是胃癌细胞 TRPM7 样电流的有效阻断剂，同时诱导细胞死亡。然而，齐留通不能抑制 TRPM7 样电流活性并诱导细胞死亡。此外，特定的瞬时受体电位阳离子通道亚家族 C，成员 3（TRPC3）抑制剂，吡唑化合物（Pyr3）和特定的黑色素瘤 TRP（TRPM4）抑制剂，9-菲咯啉，不影响 TRPM7 样电流或诱导细胞死亡。我们得出结论，TRPM7 在胃癌细胞的生长和存活中具有重要作用，可能成为胃癌治疗的潜在靶点。
