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Clin Pharmacol Ther. 2017 Jul;102(1):52-61. doi: 10.1002/cpt.639. Epub 2017 Apr 4.

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

Author information

1
Section of Cardiovascular and Pharmacological Sciences, Department of Neuroscience, Imaging and Clinical Science, "G. d'Annunzio" University, Chieti, Italy.
2
CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
3
University Hospital LB, Aragon Health Research Institute (IISAragon), CIBERehd, University of Zaragoza, Zaragoza, Spain.
4
Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.

Abstract

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) E2 levels 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.

PMID:
28139830
DOI:
10.1002/cpt.639
[Indexed for MEDLINE]

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