Low‐Dose Aspirin Acetylates Cyclooxygenase‐1 in Human Colorectal Mucosa: Implications for the Chemoprevention of Colorectal Cancer

The mechanism of action of low‐dose aspirin in the prevention of colorectal cancer (CRC) remains largely hypothetical. We aimed to compare the effects of low‐dose aspirin (100 mg/day for 7 days) given to 40 individuals undergoing CRC screening on the extent of cyclooxygenase (COX)‐1 acetylation at serine‐529 (AceCOX‐1), in blood platelets vs. colorectal mucosa, at 7 (group 1) and 24 h (group 2) after dosing. A significantly (P< 0.01) lower %AceCOX‐1 was detected in colonic and rectal mucosa (average 64%) vs. platelets (average 75%) in both groups. This effect was associated with an average 46% (P< 0.01) and 35% (P< 0.05) reduction in prostaglandin (PG) E2levels and phosphorylated S6 (p‐S6) levels, respectively. Rectal mucosal levels of p‐S6/S6 significantly (P< 0.01) correlated with PGE2. These findings demonstrate that low‐dose aspirin produces long‐lasting acetylation of COX‐1 and downregulation of p‐S6 in human colorectal mucosa, an effect that may interfere with early colorectal carcinogenesis.