Abstract

Tectochrysin (TEC), a natural flavonoid, has shown efficacy in ameliorating chronic colitis. However, its therapeutic potential in colitis-associated colon cancer (CAC) remains unclear. This study aimed to investigate the interventional effects of TEC on an AOM/DSS-induced mouse CAC model and elucidate its underlying molecular mechanisms. The CAC mice model was established by induction with AOM/DSS. Mice were treated with TEC and/or the Drp1 inhibitor Mdivi-1. Western blot, qRT-PCR, transmission electron microscopy, immunofluorescence, and luciferase reporter assays were employed to assess mitophagy activation and related signaling pathways. TEC significantly alleviated CAC progression, as evidenced by reduced tumor burden, disease activity index, and weight loss. It activated mitophagy in intestinal epithelial cells (IECs) via the Pink1/Parkin pathway and reversed Mdivi-1-induced mitophagy inhibition. Tectochrysin ameliorates CAC by activating IEC mitophagy, highlighting its potential as a therapeutic agent for CAC.