Low-dose aspirin acetylates cyclooxygenase-1 in human colorectal mucosa: implications for the chemoprevention of colorectal cancer
| Autor: | L Di Francesco, Angel Lanas, Annalisa Bruno, Melania Dovizio, Simone Schiavone, Annalisa Contursi, Paola Patrignani, Stefania Tacconelli, Carlo Patrono, Elena Piazuelo, Mirco Zucchelli, Angela Sacco, Carlos Sostres |
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| Rok vydání: | 2017 |
| Předmět: |
Blood Platelets
Male 0301 basic medicine Oncology medicine.medical_specialty Carcinogenesis Colorectal cancer Biopsy Prostaglandin Gastroenterology Dinoprostone 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Internal medicine medicine Humans Cyclooxygenase Inhibitors Pharmacology (medical) Platelet Intestinal Mucosa Phosphorylation Pharmacology Aspirin Dose-Response Relationship Drug biology business.industry Ribosomal Protein S6 Kinases Acetylation Middle Aged medicine.disease Treatment Outcome 030104 developmental biology Mechanism of action chemistry 030220 oncology & carcinogenesis Cyclooxygenase 1 biology.protein Female Cyclooxygenase medicine.symptom Colorectal Neoplasms business medicine.drug |
| Zdroj: | Zaguán. Repositorio Digital de la Universidad de Zaragoza instname |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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