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Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease
Author(s) -
Allgayer H.
Publication year - 2003
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.18.s2.1.x
Subject(s) - inflammatory bowel disease , medicine , mesalazine , cancer research , cell growth , colorectal cancer , mouse model of colorectal and intestinal cancer , aspirin , pharmacology , apoptosis , immunology , cancer , biology , disease , biochemistry
Summary 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 κB (NFκB), 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 δ (PPARδ), 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 PPARδ 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.