Gochujang elicits anti-cancer effects via distinct molecular mechanisms across different gastrointestinal cancer cell types

Gastrointestinal (GI) cancers, including gastric, hepatic, and pancreatic cancers, account for a substantial proportion of cancer-related global morbidity and mortality. Dietary habits and bioactive food components significantly influence cancer initiation and progression. As a representative Korean traditional fermented food (KTFF), Gochujang exhibits multiple health benefits, including anti-mutagenic effects; however, its detailed cellular and molecular mechanisms of anti-cancer effects across different GI cancer cell types remain unclear. The radical scavenging activity of Gochujang extract (GE) was ABTS: 2.86–31.84% and DPPH: 7.95–52.79%. In addition, total phenolic and flavonoid contents of GE were 6.94 ± 0.23 mg GAE/g and 9.28 ± 0.72 mg RE/g, respectively. GE markedly inhibited cell viability, migration, and colony formation in all GI cancer cell lines, including gastric cancer (AGS and SNU-668), hepatic cancer (HepG2 and Hep3B), and pancreatic cancer (MIA PaCa-2). Furthermore, GE markedly reduced the expression of cell proliferation-related proteins and changed the levels of apoptosis-involved proteins in AGS, Hep3B, and MIA PaCa-2 cells, indicating its multifaceted anti-cancer activity. Interestingly, GE significantly altered the expression of antioxidant enzymes and increased reactive oxygen species (ROS) production in gastric and hepatic cancer cells, but these effects of GE were not observed in pancreatic cancer cells. In conclusion, these findings demonstrate that Gochujang exerts comprehensive anti-cancer effects across gastric, hepatic, and pancreatic cancer cells through the coordinated inhibition of proliferation-, migration-, and survival-related mechanisms, while additionally regulating ROS metabolism in a distinctly cell type–specific manner.