title: Quercetin induces apoptosis by inhibiting MAPKs and TRPM7 channels in AGS cells.
abstract: The worldwide incidence and mortality rate of gastric cancer remain high, and thus, novel treatment concepts are required. Quercetin, a bioflavonoid, has been proposed to have anti-cancer properties. The aim of this study was to determine the nature of the apoptotic mechanisms responsible for the effects of quercetin on AGS cells (a commonly used human gastric adenocarcinoma cell line). AGS cell viability was assessed by MTT assay and flow cytometric analysis, mitochondrial membrane depolarization was assessed, and caspase-3 was used to determine the involvement of apoptosis. Whole-cell configuration patch-clamp experiments were used to regulate the transient receptor potential melastatin (TRPM)7 channels. To investigate the signaling pathway of quercetin-induced apoptosis in the AGS cells, western blot analysis and MTT assay were performed. Quercetin was found to induce the apoptosis of these cells, and this apoptosis was inhibited by SB203580 (a p38 kinase inhibitor), SP600125 (a JNK inhibitor) and PD98059 (an ERK inhibitor). In addition, quercetin inhibited TRPM7 currents in the AGS cells and in human embryo kidney (HEK)293 cells which overexpress TRPM7 channels. Furthermore, treatment with quercetin increased the apoptosis of HEK293 cells, which overexpress TRPM7, indicating that the upregulation of TRPM7 channels underlies quercetin-induced cell death. These results suggest that quercetin plays an important pathophysiological role in AGS cells through mitogen‑activated protein kinase (MAPK) signaling pathways and TRPM7 channels, and that quercetin has potential as a pharmacological agent for the treatment of gastric cancer.
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Min Chul
authors.initials: MC
authors.lastname: Kim
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Lim
authors.affiliation: Division of Applied Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Sung Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D050053:TRPM Cation Channels; C432165:pyrazolanthrone; D011794:Quercetin; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one