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Low‐Dose Aspirin Acetylates Cyclooxygenase‐1 in Human Colorectal Mucosa: Implications for the Chemoprevention of Colorectal Cancer
Author(s) -
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
Publication year - 2017
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.639
Subject(s) - aspirin , colorectal cancer , medicine , cyclooxygenase , gastroenterology , colorectal adenoma , acetylation , platelet , intestinal mucosa , prostaglandin , endocrinology , cancer , chemistry , enzyme , biochemistry , gene
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 2 levels and phosphorylated S6 (p‐S6) levels, respectively. Rectal mucosal levels of p‐S6/S6 significantly ( P < 0.01) correlated with PGE 2 . 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.