Molecular targets of aspirin and cancer prevention

• Published in: British journal of cancer Vol. 111; no. 1; pp. 61 - 67
• Main Authors: Alfonso, L, Ai, G, Spitale, R C, Bhat, G J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.05.2014; Nature Publishing Group
• Subjects: 631/92/609; 692/699/67/2195; 692/700/565/1436/1983; Acids; Analgesics; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anticarcinogenic Agents - pharmacology; Apoptosis; Aspirin; Aspirin - pharmacology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Colorectal cancer; Disease prevention; Drug dosages; Drug Resistance; Enzymes; Epidemiology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Medical research; Medical sciences; Molecular Medicine; Molecular Targeted Therapy; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - drug therapy; Neoplasms - prevention & control; Oncology; Pharmaceutical sciences; Pharmacy; Plasma; Review; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; United States > US; acetylation; aspirin; salicylic acid; biomolecules; colon cancer; chemoprevetion; Prostaglandin-endoperoxide synthase; Salicylic acid; Enzyme; Enzyme inhibitor; Acetylsalicylic acid; Malignant tumor; Antiplatelet agent; Targeted prevention; Colonic disease; Non steroidal antiinflammatory agent; Analgesic; Colon cancer; Cancerology; Antipyretic; Digestive diseases; Intestinal disease; Oxidoreductases; Salicylates; Acetylation; Antirheumatic agent; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.271

Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin’s anticancer effects. Aspirin’s unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug.