Pterostilbene and 3′-Hydroxypterostilbene Alleviate AOM/DSS-Induced and Chronic Jet Lag-Exacerbated Colon Cancer

Chronic circadian disruption is associated with colorectal cancer (CRC), but whether it exacerbates CRC progression and influences the protective effects of dietary interventions remains unclear. We examined pterostilbene (PSB) and 3′-hydroxypterostilbene (3′-HPSB) in an azoxymethane/dextran sulfate sodium-induced CRC mouse model exposed to chronic jet lag. Chronic jet lag aggravated disease activity, intestinal pathology, inflammation, and tumor burden. Dietary PSB and 3′-HPSB supplementations, initiated before CRC induction, attenuated these pathological changes and reduced macroscopic tumors (≥2 mm) by approximately 36% and 49%, respectively. These effects were accompanied by alterations in circadian clock-related and Wnt/β-catenin signaling-related proteins and by reduced intestinal epithelial proliferation. Supplementation was also associated with changes in gut microbiota composition and fecal short-chain fatty acid levels. These findings support preventive/protective effects of PSB and 3′-HPSB under chronic circadian disruption and identify associated molecular and microbial alterations warranting further mechanistic investigation.