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

Vollständiger Abstract

Worum geht es in dieser Arbeit?

ABSTRACT 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, KRAS G12D ‐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.