Non-steroidal anti-inflammatory drugs and molecular carcinogenesis of colorectal carcinomas

Novel etodolac analog SDX-308 (CEP-18082) induces cytotoxicity in multiple myeloma cells associated with inhibition of β-catenin/TCF pathway

“…Recently, attention has been focused on the antiproliferative activity of NSAIDs and their potential utility as chemopreventive and antitumor agents. 2,36,37 The long-term ingestion of various NSAIDs is associated with a reduced incidence of colorectal, 37 esophageal, 38 gastric, 39 prostate, lung and breast cancer. 2,40 To date, however, the mechanisms underlying the effects of these drugs on cancer cells are not fully defined.…”

Apc Deficiency Is Associated with Increased Egfr Activity in the Intestinal Enterocytes and Adenomas of C57BL/6J-Min/+ Mice

“…Intestinal adenomas in mouse CRC models grow in a microenvironment that contains high Cox-2 activity, likely produced by stromal fibroblasts and endothelial cells (76). Targeted deletion of the murine Cox-2 gene (Ptgs-2) virtually eliminated Apc-dependent tumor formation (15) and suppression of Cox-2 activity by NSAIDs prevented tumor growth and/or induced their regression in mice and humans (8,16). Moreover, the important role of PGE 2 in promoting adenoma formation in Min/ϩ mice was emphasized when an E prostaglandin receptor agonist attenuated the suppressive effects of NSAIDs on tumor growth (77).…”

“…Synergistic inhibition of Min/ϩ tumor multiplicity was found in another study that examined the effect of a combination chemoprevention regimen with the NSAID, sulindac, and another selective EGFR inhibitor, EKI-569 (14). NSAIDs likely achieve tumor prevention by inhibition of Cox-2, a well established tumor promoter in mouse models of CRC (15) and in human tumors (16,17). Cox-2 activity induces the inflammatory prostaglandin, PGE 2 , and the enhanced efficacy of NSAIDs in combination with receptor-tyrosine kinase (RTK) inhibitors (14) may relate to the finding that PGE 2 can transactivate EGFR in intestinal epithelial cells (18,19).…”

Current overview of colitis-associated colorectal cancer

“…The intake of NSAIDs may reduce the risk of CACRC development, but their application is limited due to severe adverse effects in the gastrointestinal system, including gastric ulcers [52]. Furthermore, some studies revealed that not all NSAIDs, e.g.…”