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Some flavonoids have been reported to enhance metal-catalyzed Fenton reactions, leading to excessive reactive oxygen species (ROS) and oxidative stress. Procyanidin B2 (PB2) is a plant-derived flavonoid whose anticancer activity has been attributed to inhibition of tumorigenesis-related signaling pathways in previous studies. However, the role of oxidative stress in the therapeutic activity of PB2 against gastric cancer remains unexplored. Beyond evaluating the anticancer potential of PB2 in proliferation, migration, cell death, and immune cell recruitment, we concentrated on alterations in intracellular redox state following PB2 treatment in gastric cancer cells. Through metabolomic and transcriptomic screening, we identified pathways altered by PB2 in gastric cancer cells, focusing on oxidative stress related biological functions, which were further confirmed through in vitro and in vivo validation. The heightened oxidative levels resulting from PB2 treatment induce endoplasmic reticulum stress and promote apoptosis. Furthermore, PB2 enhances autophagic flux to increase cellular free iron and promote ferroptosis. All in all, our research provides a comprehensive perspective on the therapeutic potential of PB2 in treating gastric cancer, demonstrating its capacity to inhibit growth signals and induce oxidative stress-related cell death.
Li et al. (Mon,) studied this question.