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New Insights into the Mechanism of Action of Aspirin in the Prevention of Colorectal Neoplasia

[ Vol. 21 , Issue. 35 ]

Author(s):

Luigia Di Francesco, Luilli Antonio López Contreras, Angela Sacco and Paola Patrignani   Pages 5116 - 5126 ( 11 )

Abstract:


The results of clinical studies have shown that the chronic administration of aspirin, even at the lowdoses (75-100 mg daily) recommended for the prevention of cardiovascular disease, is associated with a reduction of cancer incidence and mortality, in particular colorectal cancer (CRC). The mechanism of action of aspirin as an antineoplastic agent remains controversial. However, data of clinical pharmacology and several features of the chemopreventive effect of aspirin, emerged from clinical trials, suggest that the antiplatelet effect of aspirin plays a central role in its anticancer effects. In addition to their contribution to tumor metastasis, platelets may play a role in the early phases of tumorigenesis. In response to lifestyle and environment factors, intestinal epithelial damage/ dysfunction may be associated with platelet activation, initially as a mechanism to repair the damage. However, if the platelet response is unconstrained, it may contribute to the development of chronic inflammation. Altogether these events lead to alter the normal functions of intestinal epithelial cells and may translate into cellular transformation through several mechanisms, including the overexpression of cyclooxygenase(COX)-2 and epidermal growth factor receptor (EGFR), which are considered early events in colorectal tumorigenesis. Thus, antiplatelet agents may play a role in the prevention of CRC by modifying epigenetic events involved in early phases of colorectal tumorigenesis. Finally, we carried out a critical review of the literature on off-target mechanisms of aspirin action as anticancer drug.

Keywords:

Aspirin, coxibs, platelets, colorectal cancer, metastasis, cyclooxygenases, thromboxane A2, prostaglandin E2.

Affiliation:

Department of Neuroscience, Imaging and Clinical Sciences and Center of Excellence on Aging .(CeSI), “G. d’Annunzio” University, Via deiVestini, 31, 66100, Chieti, Italy



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