Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease.
A series of epidemiological, experimental and preliminary clinical trials strongly suggest that mesalazine or 5-aminosalicyclic acid (5-ASA) may have antineoplastic and potentially prophylactic chemopreventive properties. It is assumed that mesalazine may have similar genetic and molecular targets as nonsteroidal anti-inflammatory drugs (NSAIDs), which is further supported by its close similarity with aspirin, differing only in its structure by the presence of an amino group at position 5 of the benzene ring. The putative chemopreventive actions include the inhibition of inflammatory cascades and/or reactions involved in cell growth and proliferation, such as cyclo-oxygenase (COX-1 and COX-2), which regulate cell proliferation through the formation of prostaglandins; lipoxygenase; nuclear factor kappaB (NFkappaB), responsible for the subsequent expression of pro-inflammatory molecules; MAP kinases and Bcl-2, as well as the activation of apoptotic processes, such as the stimulation of intestinal sphingomyelinase. The peroxisome-proliferator-activated receptor delta (PPARdelta), which also regulates gene transcription, is thought to play a role in both inflammatory and non-inflammatory driven carcinogenesis. This may be another significant target. It is hypothesized that 5-ASAs may prevent the enhancing effect of prostaglandins on PPARdelta binding to DNA by its COX inhibitory properties, decreasing proliferation of colorectal mucosal cells in non-inflammatory bowel disease patients with sporadic polyps of the large bowel.
Allgayer
H
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Oncology Department, Rehaklinik ob der Tauber der LVA Baden-Württemberg, Academic Teaching Hospital of the University of Heidelberg, Heidelberg, Germany. allgayer@reha-klinik-odt.de
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004249:DNA Damage; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D019804:Mesalamine / Q000627:therapeutic use*; D011451:Prostaglandin-Endoperoxide Synthases; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D019804:Mesalamine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases