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Molecular and Experimental Basis for COX Inhibition in Cancer

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NSAIDs and Aspirin

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Abstract

A growing body of evidences suggests that aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) cause anticancer effects, mainly in the colorectum. At therapeutic doses, these agents act through the inhibition of cyclooxygenase (COX)-1 and COX-2, and, in turn, they affect the biosynthesis of prostanoids. Interestingly, the cancer chemopreventive effect was also found with low-dose aspirin, which is used to prevent cardiovascular disease for its preferential inhibitory effect on platelet COX-1. This finding led to hypothesize that the antiplatelet effect of aspirin is involved in its cancer chemopreventive action. In fact, it has been proposed that activated platelets, in response to tissue damage, may induce a pro-inflammatory program in tumor microenvironment involving enhanced biosynthesis of COX-2-dependent prostaglandin E2, a pro-inflammatory and protumorigenic prostanoid. Selective inhibitors of COX-2 (named coxibs) significantly reduce the risk of recurrent colorectal adenomas, but they may enhance the risk of cardiovascular events, thus precluding their use as anticancer agents. Importantly, the inhibition of platelet function by low-dose aspirin my also prevent tumor metastasis. In fact, within the circulatory system, the formation of platelet aggregates surrounding tumor cells will support tumor cell survival and protection from immune elimination and promote their arrest at the endothelium and extravasation. Aspirin and other NSAIDs are able to affect proliferation and to induce apoptosis of colon cancer cells in vitro, independently from their inhibitory effect on COX-dependent prostanoid biosynthesis, at very high concentrations, often in the millimolar range, that are not reached in the systemic circulation, at therapeutic doses.

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  1. Department of Neuroscience, Imaging and Clinical Science, Section of Cardiovascular and Pharmacological Sciences, CeSI-MeT, “G. d’Annunzio” University School of Medicine, Chieti, Italy

    Annalisa Bruno Ph.D., Melania Dovizio Ph.D. & Paola Patrignani Ph.D.

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    Angel Lanas

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Bruno, A., Dovizio, M., Patrignani, P. (2016). Molecular and Experimental Basis for COX Inhibition in Cancer. In: Lanas, A. (eds) NSAIDs and Aspirin. Springer, Cham. https://doi.org/10.1007/978-3-319-33889-7_12

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