Document Detail

Cyclooxygenase-2-dependent and -independent inhibition of proliferation of colon cancer cells by 5-aminosalicylic acid.
MedLine Citation:
PMID:  17981262     Owner:  NLM     Status:  MEDLINE    
The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway may have a pathogenic role in colorectal cancer (CRC). Recent studies suggest that 5-aminosalicylic acid (5-ASA) reduces the risk of inflammatory bowel disease-related CRC, but the mechanism by which 5-ASA interferes with CRC cell growth remains unknown. In this study, we have examined whether the negative effect of 5-ASA on CRC cells is dependent on COX-2/PGE2 axis inhibition. We show that 5-ASA down-regulates both constitutive and TNF-alpha or IL-1beta-induced COX-2 in HT-115 and HT-29 cells. Inhibition of COX-2 by 5-ASA occurs at the RNA and protein level, and is associated with a significant decrease in PGE2 synthesis, arrest of growth and enhanced death of CRC cells. However, exogenous PGE2 does not revert the 5-ASA-mediated CRC cell proliferation block. 5-ASA also inhibits the growth of DLD-1, a COX-deficient CRC cell line, thus suggesting that the anti-proliferative effect of 5-ASA on CRC cells is not strictly dependent on the inhibition of COX-2/PGE2. Taken together our data indicate that 5-ASA causes both a COX-2-dependent and -independent inhibition of CRC cell growth.
Carmine Stolfi; Daniele Fina; Roberta Caruso; Flavio Caprioli; Massimiliano Sarra; Massimo Claudio Fantini; Angelamaria Rizzo; Francesco Pallone; Giovanni Monteleone
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-29
Journal Detail:
Title:  Biochemical pharmacology     Volume:  75     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-15     Completed Date:  2008-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  668-76     Citation Subset:  IM    
Dipartimento di Medicina Interna, Università Tor Vergata, Via Montpellier, 1-00133 Rome, Italy.
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MeSH Terms
Apoptosis / drug effects
Cell Line, Tumor
Colonic Neoplasms / drug therapy*,  enzymology,  pathology
Cyclooxygenase 2 / genetics,  physiology*
Cyclooxygenase 2 Inhibitors / pharmacology*
Dinoprostone / biosynthesis
Dose-Response Relationship, Drug
Interleukin-1beta / pharmacology
Mesalamine / pharmacology*
Transforming Growth Factor alpha / pharmacology
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 0/Interleukin-1beta; 0/Transforming Growth Factor alpha; 363-24-6/Dinoprostone; 89-57-6/Mesalamine; EC 2

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