{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:20:16Z","timestamp":1790882416681,"version":"4.1.0"},"reference-count":110,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008213","name":"South Dakota State University","doi-asserted-by":"publisher","award":["Pilot research grant"],"award-info":[{"award-number":["Pilot research grant"]}],"id":[{"id":"10.13039\/100008213","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and fever, and in the prevention of thrombotic cardiovascular diseases. Its anti-inflammatory and cardio-protective actions have been well studied and occur through inhibition of cyclooxygenases (COX). Interestingly, a vast amount of epidemiological, preclinical and clinical studies have revealed aspirin as a promising chemopreventive agent, particularly against colorectal cancers (CRC); however, the primary mechanism by which it decreases the occurrences of CRC has still not been established. Numerous mechanisms have been proposed for aspirin\u2019s chemopreventive properties among which the inhibition of COX enzymes has been widely discussed. Despite the wide attention COX-inhibition has received as the most probable mechanism of cancer prevention by aspirin, it is clear that aspirin targets many other proteins and pathways, suggesting that these extra-COX targets may also be equally important in preventing CRC. In this review, we discuss the COX-dependent and -independent pathways described in literature for aspirin\u2019s anti-cancer effects and highlight the strengths and limitations of the proposed mechanisms. Additionally, we emphasize the potential role of the metabolites of aspirin and salicylic acid (generated in the gut through microbial biotransformation) in contributing to aspirin\u2019s chemopreventive actions. We suggest that the preferential chemopreventive effect of aspirin against CRC may be related to direct exposure of aspirin\/salicylic acid or its metabolites to the colorectal tissues. Future investigations should shed light on the role of aspirin, its metabolites and the role of the gut microbiota in cancer prevention against CRC.<\/jats:p>","DOI":"10.3390\/ijms21239018","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T09:16:49Z","timestamp":1606468609000},"page":"9018","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Mechanisms of Colorectal Cancer Prevention by Aspirin\u2014A Literature Review and Perspective on the Role of COX-Dependent and -Independent Pathways"],"prefix":"10.3390","volume":"21","author":[{"given":"Ranjini","family":"Sankaranarayanan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences and Translational Cancer Research Center, College of Pharmacy and Allied Health Professions, South Dakota State University, Brookings, SD 57007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Ramesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Entomology, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meric A.","family":"Altinoz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Acibadem M.A.A. University, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Jayarama","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Translational Cancer Research Center, College of Pharmacy and Allied Health Professions, South Dakota State University, Brookings, SD 57007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3390\/cancers5020676","article-title":"Epigenetics and colorectal cancer pathogenesis","volume":"5","author":"Bardhan","year":"2013","journal-title":"Cancers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3322\/caac.21601","article-title":"Colorectal cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. 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