The role of transient receptor potential channel blockers in human gastric cancer cell viability.
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.
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
Byung Joo
BJ
Kim
Sung-Young
SY
Kim
Sanghoon
S
Lee
Ju-Hong
JH
Jeon
Hirofumi
H
Matsui
Young Kyu
YK
Kwon
Seon Jeong
SJ
Kim
Insuk
I
So
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008564:Membrane Potentials; D017346:Protein Serine-Threonine Kinases; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D000970:Antineoplastic Agents; D016859:Lipoxygenase Inhibitors; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D001094:Arachidonate 5-Lipoxygenase; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human