Studies with the Min and APC-knockout mice provide the strongest evidence to date that the enzyme cyclooxygenase-2 plays a major role in colon carcinogenesis, and that nonsteroidal anti-inflammatory drugs that target cyclooxygenase-2 have great potential as colon cancer chemopreventive agents.
Relative to aspirin, APHS was 60 times as reactive against COX-2 and 100 times as selective for its inhibition; it also inhibited COX-2 in cultured macrophages and colon cancer cells and in the rat air pouch in vivo.
Here, we report that flufenamic acid shows two opposing effects on COX-2 expression; it induces COX-2 expression in the colon cancer cell line (HT-29) and macrophage cell line (RAW 264.7); conversely, it inhibits tumor necrosis factor alpha (TNFalpha)- or lipopolysaccharide (LPS)-induced COX-2 expression.
As COX-2 and PGE(2) are known promoters of gastrointestinal cancer, these data suggest that M(3) receptor activation may facilitate progression of colon carcinoma, in part by a COX-2-mediated cellular mechanism.
We evaluated the effect of cyclooxygenase (COX) inhibitors (NSAIDs) on human colon carcinoma cells (HCA-7) and identified several genes that are regulated after treatment with NS-398, a selective COX-2 inhibitor.
Nonsteroidal anti-inflammatory drugs reduce the risk of colon cancer and this effect is mediated in part through inhibition of type 2 prostaglandin endoperoxide synthase/ cyclo-oxygenase (COX-2).
Nonsteroidal antiinflammatory drugs inhibiting cyclooxygenase (COX) enzyme activity in both its constitutive (COX-1) and inducible (COX-2) isoforms were shown also to inhibit the development of colon carcinoma in animal models.
Cyclooxygenase-2 (COX-2), which catalyzes the rate-limiting step in the synthesis of prostaglandins from arachidonic acids, is known to be up-regulated in colon cancer, and multiple lines of evidence indicate that it is a critical early step in colon carcinogenesis.
To understand the molecular nature of enhanced COX-2 expression detected in colon cancer, we examined the ability of the AU-rich element-containing (ARE-containing) 3' untranslated region (3'UTR) of COX-2 mRNA to regulate rapid mRNA decay in human colon cancer cells.
Numerous studies have demonstrated that prostaglandin H synthase-2 (PHS-2) is involved in gastrointestinal carcinogenesis, and that nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit PHS, can reduce the risk of colon cancer.
Results of several studies using mouse models of colon cancer and the results of clinical trials have shown COX-2 to be a useful target for the prevention and treatment of colon cancer.
Prostaglandin H synthase 2 (also known as cyclooxygenase-2) is thought to play a role in the prevention of colon cancer by aspirin, an inhibitor of the enzyme.
In this study, effects of sodium butyrate on the promoter-dependent transcriptional activity of iNOS and COX-2 genes were investigated in a colon cancer cell line, DLD-1, using a reporter gene assay system.
It is known that nitric oxide activates the cyclooxygenase 2 enzyme, which plays a pivotal role in the progression of colon cancer via prostaglandin synthesis and angiogenesis.
This indicates that NF-kappaB activated by NS-398 is transcriptionally inactive and is an encouraging result for the use of COX-2-selective NSAIDs not only in chemoprevention but also as novel therapies for colon cancer.