Kim Min Chul, Lee Hee Jung, Lim Bora, Ha Ki-Tae, Kim Sung Young, So Insuk, Kim Byung Joo
Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
Division of Applied Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
Int J Mol Med. 2014 Jun;33(6):1657-63. doi: 10.3892/ijmm.2014.1704. Epub 2014 Mar 18.
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.
全球胃癌的发病率和死亡率仍然很高，因此需要新的治疗理念。槲皮素是一种生物类黄酮，已被认为具有抗癌特性。本研究的目的是确定负责槲皮素对AGS细胞（一种常用的人胃腺癌细胞系）作用的凋亡机制的性质。通过MTT法和流式细胞术分析评估AGS细胞活力，评估线粒体膜去极化，并使用caspase-3确定凋亡的参与情况。采用全细胞配置膜片钳实验来调节瞬时受体电位褪黑素（TRPM）7通道。为了研究槲皮素诱导AGS细胞凋亡的信号通路，进行了蛋白质免疫印迹分析和MTT法检测。发现槲皮素可诱导这些细胞凋亡，并且SB203580（一种p38激酶抑制剂）、SP600125（一种JNK抑制剂）和PD98059（一种ERK抑制剂）可抑制这种凋亡。此外，槲皮素抑制AGS细胞和过表达TRPM7通道的人胚肾（HEK）293细胞中的TRPM7电流。此外，用槲皮素处理可增加过表达TRPM7的HEK293细胞的凋亡，表明TRPM7通道的上调是槲皮素诱导细胞死亡的基础。这些结果表明，槲皮素通过丝裂原活化蛋白激酶（MAPK）信号通路和TRPM7通道在AGS细胞中发挥重要的病理生理作用，并且槲皮素具有作为治疗胃癌的药物的潜力。
