Low-dose aspirin acetylates cyclooxygenase-1 in human colorectal mucosa: implications for the chemoprevention of colorectal cancer.
Resumen: 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 hours (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 down-regulation of p-S6 in human colorectal mucosa, an effect that may interfere with early colorectal carcinogenesis.
Idioma: Inglés
DOI: 10.1002/cpt.639
Año: 2017
Publicado en: CLINICAL PHARMACOLOGY & THERAPEUTICS 36 (2017), [29 pp.]
ISSN: 0009-9236

Factor impacto JCR: 6.544 (2017)
Categ. JCR: PHARMACOLOGY & PHARMACY rank: 13 / 261 = 0.05 (2017) - Q1 - T1
Factor impacto SCIMAGO: 1.699 - Pharmacology (medical) (Q1) - Pharmacology (Q1)

Tipo y forma: Article (PostPrint)
Área (Departamento): Área Fisiología (Dpto. Farmacología y Fisiolog.)
Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)


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