ISSN:
1365-2036
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2036.18.s2.1.x
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