Jiang Jun, Li Deming, Li Fan, Li Huanqing, Zhang Xiaohong, Feng Li
Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China.
Mol Cell Biochem. 2025 May;480(5):3201-3215. doi: 10.1007/s11010-024-05138-2. Epub 2024 Nov 20.
Catechin, a polyphenolic compound in various foods and beverages, shows strong anti-cancer effects against gastric cancer (GC) cells. This study explored the effect of catechin on GC cell apoptosis and endoplasmic reticulum (ER) stress. GC cells were treated with different catechin concentrations to assess effects on cell viability, LDH release, invasion, migration, apoptosis, intracellular calcium (Ca⁺), ER stress markers, and reactive oxygen species (ROS). siRNA knockdown targeted GRP78, PERK, CHOP, and NOX4 to examine their roles in catechin-induced ER stress and apoptosis. Catechin treatment significantly reduced GC cell viability, increased LDH release, and induced apoptosis dose-dependently. Catechins elevated intracellular Ca⁺ and ER stress markers. Co-treatment with thapsigargin (TG) intensified these effects, implicating ER stress in apoptosis. Knocking down GRP78, PERK, and CHOP mitigated catechin-induced apoptosis and restored viability. Additionally, catechins raised ROS levels, while co-treatment with Diphenyleneiodonium (DPI) or N-acetylcysteine (NAC) lowered ROS, cell damage, and ER stress markers. NOX4 knockdown countered catechin-induced viability loss and upregulated CHOP and cleaved caspase-3. Catechin induces apoptosis in GC cells through ER stress and ROS generation. Key mediators include GRP78, PERK, CHOP, and NOX4, suggesting potential therapeutic targets for enhancing catechin efficacy in GC treatment.
儿茶素是各种食品和饮料中的一种多酚类化合物，对胃癌（GC）细胞具有很强的抗癌作用。本研究探讨了儿茶素对GC细胞凋亡和内质网（ER）应激的影响。用不同浓度的儿茶素处理GC细胞，以评估其对细胞活力、乳酸脱氢酶（LDH）释放、侵袭、迁移、凋亡、细胞内钙（Ca⁺）、ER应激标志物和活性氧（ROS）的影响。使用小干扰RNA（siRNA）敲低葡萄糖调节蛋白78（GRP78）、蛋白激酶R样内质网激酶（PERK）、C/EBP同源蛋白（CHOP）和NADPH氧化酶4（NOX4），以研究它们在儿茶素诱导的ER应激和凋亡中的作用。儿茶素处理显著降低了GC细胞活力，增加了LDH释放，并剂量依赖性地诱导凋亡。儿茶素升高了细胞内Ca⁺和ER应激标志物。与毒胡萝卜素（TG）共同处理增强了这些作用，提示ER应激参与凋亡。敲低GRP78、PERK和CHOP可减轻儿茶素诱导的凋亡并恢复细胞活力。此外，儿茶素提高了ROS水平，而与二亚苯基碘鎓（DPI）或N-乙酰半胱氨酸（NAC）共同处理可降低ROS、细胞损伤和ER应激标志物。敲低NOX4可对抗儿茶素诱导的细胞活力丧失，并上调CHOP和裂解的半胱天冬酶-3。儿茶素通过ER应激和ROS生成诱导GC细胞凋亡。关键介质包括GRP78、PERK、CHOP和NOX4，提示它们可能是增强儿茶素在GC治疗中疗效的潜在治疗靶点。
