Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease.
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Allgayer H
Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease.
Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4.
- PubMed ID
- 12950415 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Aminosalicylic acid Inhibitor of nuclear factor kappa-B kinase subunit alpha Protein Humans UnknownInhibitorDetails Balsalazide Prostaglandin G/H synthase 1 Protein Humans YesInhibitorDetails Balsalazide Prostaglandin G/H synthase 2 Protein Humans YesInhibitorDetails Mesalazine Inhibitor of nuclear factor kappa-B kinase subunit alpha Protein Humans UnknownInhibitorDetails Mesalazine Inhibitor of nuclear factor kappa-B kinase subunit beta Protein Humans UnknownInhibitorDetails Mesalazine Prostaglandin G/H synthase 1 Protein Humans YesInhibitorDetails Olsalazine Human Cyclooxygenases (Protein Group) Protein group Humans YesInhibitorDetails Sulfasalazine Inhibitor of nuclear factor kappa-B kinase subunit alpha Protein Humans UnknownNot Available Details Sulfasalazine Inhibitor of nuclear factor kappa-B kinase subunit beta Protein Humans YesInhibitorDetails Sulfasalazine Prostaglandin G/H synthase 1 Protein Humans YesInhibitorDetails