Low-dose aspirin acetylates cyclooxygenase-1 in human colorectal mucosa: implications for the chemoprevention of colorectal cancer.

Patrignani, P ; Sacco, A ; Sostres, C ; Bruno, A ; Dovizio, M ; Piazuelo, E (Universidad de Zaragoza) ; Di Francesco, L ; Contursi, A ; Zucchelli, M ; Schiavone, S ; Tacconelli, S ; Patrono, C ; Lanas, A. (Universidad de Zaragoza)

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.)