Catechin promotes endoplasmic reticulum stress-mediated gastric cancer cell apoptosis via NOX4-induced reactive oxygen species.

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.