Graduate Institute of Clinical of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.
Quercetin is one of the natural components from natural plant and it induces cell apoptosis in many human cancer cell lines. However, no available reports show that quercetin induces apoptosis and altered associated gene expressions in human gastric cancer cells, thus, we investigated the effect of quercetin on the apoptotic cell death and associated gene expression in human gastric cancer AGS cells. Results indicated that quercetin induced cell morphological changes and reduced total viability via apoptotic cell death in AGS cells. Furthermore, results from flow cytometric assay indicated that quercetin increased reactive oxygen species (ROS) production, decreased the levels of mitochondrial membrane potential (ΔΨ ), and increased the apoptotic cell number in AGS cells. Results from western blotting showed that quercetin decreased anti-apoptotic protein of Mcl-1, Bcl-2, and Bcl-x but increased pro-apoptotic protein of Bad, Bax, and Bid. Furthermore, quercetin increased the gene expressions of TNFRSF10D (Tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain), TP53INP1 (tumor protein p53 inducible nuclear protein 1), and JUNB (jun B proto-oncogene) but decreased the gene expression of VEGFB (vascular endothelial growth factor B), CDK10 (cyclin-dependent kinase 10), and KDELC2 (KDEL [Lys-Asp-Glu-Leu] containing 2) that are associated with apoptosis pathways. Thus, those findings may offer more information regarding the molecular, gene expression, and signaling pathway for quercetin induced apoptotic cell death in human gastric cancer cells.
槲皮素是天然植物中的一种天然成分，它能诱导许多人类癌细胞系发生细胞凋亡。然而，目前尚无报道表明槲皮素能诱导人类胃癌细胞发生凋亡，并改变相关基因的表达，因此，我们研究了槲皮素对人胃癌 AGS 细胞凋亡和相关基因表达的影响。结果表明，槲皮素通过诱导 AGS 细胞发生凋亡性细胞死亡，导致细胞形态发生变化，总活力降低。此外，流式细胞术检测结果表明，槲皮素能增加活性氧（ROS）的产生，降低线粒体膜电位（ΔΨ）水平，并增加 AGS 细胞中的凋亡细胞数量。Western blot 结果表明，槲皮素降低了抗凋亡蛋白 Mcl-1、Bcl-2 和 Bcl-x 的表达，但增加了促凋亡蛋白 Bad、Bax 和 Bid 的表达。此外，槲皮素增加了 TNFRSF10D（肿瘤坏死因子受体超家族成员 10d，截断死亡结构域的诱饵）、TP53INP1（肿瘤蛋白 p53 诱导核蛋白 1）和 JUNB（jun B 原癌基因）的基因表达，而降低了 VEGFB（血管内皮生长因子 B）、CDK10（细胞周期蛋白依赖性激酶 10）和 KDELC2（含 KDEL [Lys-Asp-Glu-Leu]的 2 号）的基因表达，这些基因与凋亡途径有关。因此，这些发现可能为槲皮素诱导人类胃癌细胞凋亡的分子、基因表达和信号通路提供更多信息。
