Mechanistic and Pharmacological Issues of Aspirin as an Anticancer Agent

• DOI: 10.3390/ph5121346
• Publication Date: 2012-12-05T17:46:59Z
• Authors: Melania Dovizio; Stefania Tacconelli; Carlos Sostres; Emanuela Ricciotti; Paola Patrignani
• Keywords: platelet; RS1-441; 0303 health sciences; 03 medical and health sciences; Pharmacy and materia medica; aspirin; R; Medicine; colorectal cancer; Review; cycloooxygenase-1; 3. Good health

Recent findings have shown that aspirin, taken for several years, reduces the long-term risk of some cancers, particularly colorectal cancer. The result that aspirin benefit is detectable at daily low-doses (at least 75mg), the same used for the prevention of cardiovascular disease, positions the antiplatelet action of aspirin at the center of its antitumor efficacy. At low-doses given every 24 h, aspirin is acting by a complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in the pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (approximately 20 min); nucleated cells have the ability to resynthesize the acetylated COX-isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin, such as the inhibition of Wnt/ b-catenin and NF-kB signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemo-preventive effects, but their relevance remains to be demonstrated in vivo at clinical doses. In conclusion, the results of clinical pharmacology and the analysis of randomized and epidemiological studies suggest that colorectal cancer and atherothrombosis share a common mechanism of disease, i.e. enhanced platelet activation in response to injury at distinct sites.