Dietary-Derived Corchorus olitorius L. Extract Suppresses KRAS-Mutant Pancreatic Cancer by Activating Ferritinophagy-Dependent Ferroptosis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by frequent activating mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) and limited therapeutic options. Corchorus olitorius L., a traditional edible plant widely consumed in Asia, possesses documented anti-inflammatory properties; however, its anticancer potential remains unclear. This study investigated whether Corchorus olitorius L. leaf extract (COE) induces ferroptosis in KRAS-mutant pancreatic cancer cells. The chemical composition of COE was characterized using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. A total of 11 compounds were identified, among which quercetin-3-O-glucoside was the most abundant. In our study, KRASG12D-mutant PANC1 cells exhibited greater resistance to ferroptosis than KRAS wild-type BXPC3 cells. COE increased reactive oxygen species production and intracellular iron accumulation while suppressing antioxidant defenses, particularly in KRAS-mutant PANC1 cells. Mechanistically, COE enhanced nuclear receptor coactivator 4-mediated ferritinophagy and downregulated KRAS and glutathione peroxidase 4 expression. In PANC1 xenografts, oral administration of COE significantly inhibited tumor growth and increased iron accumulation within tumor tissues. Collectively, COE induces ferroptosis in KRAS-mutant pancreatic cancer by disrupting redox homeostasis and activating ferritinophagy. These findings support the potential of COE as a dietary-derived therapeutic strategy for KRAS-driven PDAC. PRACTICAL APPLICATIONS: Corchorus olitorius L. leaf extract (COE), a commonly consumed edible plant, may serve as a functional food with potential anticancer benefits, particularly for KRAS-mutant pancreatic cancer. By promoting cancer cell death through disruption of oxidative balance and iron metabolism, COE may represent a promising food-based therapeutic strategy.