title: Low-Dose Aspirin Acetylates Cyclooxygenase-1 in Human Colorectal Mucosa: Implications for the Chemoprevention of Colorectal Cancer.
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) E2levels 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.
authors.affiliation: Section of Cardiovascular and Pharmacological Sciences, Department of Neuroscience, Imaging and Clinical Science, "G. d'Annunzio" University, Chieti, Italy.|CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Patrignani
authors.affiliation: Section of Cardiovascular and Pharmacological Sciences, Department of Neuroscience, Imaging and Clinical Science, "G. d'Annunzio" University, Chieti, Italy.|CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sacco
authors.affiliation: University Hospital LB, Aragon Health Research Institute (IISAragon), CIBERehd, University of Zaragoza, Zaragoza, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Sostres
authors.affiliation: Section of Cardiovascular and Pharmacological Sciences, Department of Neuroscience, Imaging and Clinical Science, "G. d'Annunzio" University, Chieti, Italy.|CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bruno
authors.affiliation: Section of Cardiovascular and Pharmacological Sciences, Department of Neuroscience, Imaging and Clinical Science, "G. d'Annunzio" University, Chieti, Italy.|CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Dovizio
authors.affiliation: University Hospital LB, Aragon Health Research Institute (IISAragon), CIBERehd, University of Zaragoza, Zaragoza, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Piazuelo
authors.affiliation: Section of Cardiovascular and Pharmacological Sciences, Department of Neuroscience, Imaging and Clinical Science, "G. d'Annunzio" University, Chieti, Italy.|CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Di Francesco
authors.affiliation: Section of Cardiovascular and Pharmacological Sciences, Department of Neuroscience, Imaging and Clinical Science, "G. d'Annunzio" University, Chieti, Italy.|CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Contursi
authors.affiliation: CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zucchelli
authors.affiliation: Section of Cardiovascular and Pharmacological Sciences, Department of Neuroscience, Imaging and Clinical Science, "G. d'Annunzio" University, Chieti, Italy.|CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Schiavone
authors.affiliation: Section of Cardiovascular and Pharmacological Sciences, Department of Neuroscience, Imaging and Clinical Science, "G. d'Annunzio" University, Chieti, Italy.|CeSI-MeT (Centro Scienze dell' Invecchiamento e Medicina Traslazionale), "G. d'Annunzio" University, Chieti, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Tacconelli
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Patrono
authors.affiliation: University Hospital LB, Aragon Health Research Institute (IISAragon), CIBERehd, University of Zaragoza, Zaragoza, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Lanas
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics; D001706:Biopsy / Q000379:methods; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1; D019893:Ribosomal Protein S6 Kinases; D015232:Dinoprostone; D001241:Aspirin