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

• Published in: Clinical pharmacology and therapeutics Vol. 102; no. 1; p. 52
• Main Authors: Patrignani, P, Sacco, A, Sostres, C, Bruno, A, Dovizio, M, Piazuelo, E, Di Francesco, L, Contursi, A, Zucchelli, M, Schiavone, S, Tacconelli, S, Patrono, C, Lanas, A
• Format: Journal Article
• Language: English
• Published: United States 01.07.2017
• Subjects: Acetylation - drug effects; Aspirin - administration & dosage; Aspirin - pharmacokinetics; Biopsy - methods; Blood Platelets - drug effects; Blood Platelets - enzymology; Carcinogenesis - drug effects; Carcinogenesis - metabolism; Colorectal Neoplasms - blood; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - pathology; Colorectal Neoplasms - prevention & control; Cyclooxygenase 1 - metabolism; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacokinetics; Dinoprostone - biosynthesis; Dose-Response Relationship, Drug; Female; Humans; Intestinal Mucosa - drug effects; Intestinal Mucosa - enzymology; Male; Middle Aged; Phosphorylation - drug effects; Ribosomal Protein S6 Kinases - metabolism; Treatment Outcome
• ISSN: 1532-6535
• DOI: 10.1002/cpt.639

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) E levels and phosphorylated S6 (p-S6) levels, respectively. Rectal mucosal levels of p-S6/S6 significantly (P < 0.01) correlated with PGE . 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.