Aberrant CpG island methylation, and subsequent silencing of the COX-2 promoter, has been observed in human cancer cell lines and in some human tumors of the gastrointestinal tract.
Aberrant upregulation of COX-2 enzyme resulting in accumulation of PGE2 in a cancer cell environment is a marker for progression of many cancers, including breast cancer.
Among nonsteroidal anti-inflammatory drugs (NSAIDs), licofelone is a triple inhibitor of both cyclooxygenases (COX-1 and COX-2) and of 5-lipooxygenase (5-LOX) that has shown some encouraging results in cancer prevention models.
Among them, compound A33 displayed the most potency against cancer cell lines (IC<sub>50</sub> = 6.43-10.97 μM for F10, HeLa, A549 and MCF-7 cells), lower toxicity to non-cancer cells than celecoxib (A33: IC<sub>50</sub> = 194.01 μM vs.celecoxib: IC<sub>50</sub> = 97.87 μM for 293T cells), and excellent inhibitory activities on COX-2 (IC<sub>50</sub> = 0.17 μM) and 5-LOX (IC<sub>50</sub> = 0.68 μM).
Because the IGF-1R/Akt pathway is a common upstream regulator of p70S6K, HIF-1α, and COX-2, we hypothesized that glucosamine inhibits cancer cell proliferation through this pathway.
Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in the cancer tissue and similarly COX-2 mRNA and protein were found in most of cancers and in the HP infected antral mucosa but not in HP eradicated patients in whom only cancer tissue but not gastric mucosa expressed COX-2.
Both gastrin and CCKB-R mRNA were detected in the cancer tissue and at the resection margin and similarly COX-2 mRNA was expressed in most cancers and resection margin but not in bronchial mucosa where only COX-1 was found.
Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention.
Collectively, these results suggest that overexpression of COX-2 is a frequent phenomenon in hypopharyngeal carcinoma and may play a role in tumorigenesis of this cancer.
Conventional nonsteroidal antiinflammatory drugs (NSAIDs) and recently developed COX-2-specific inhibitors have shown considerable promise in prevention of some forms of human cancer; however, its application is limited due to severe toxic side effects on normal cells.
Cyclooxygenase (COX)-2 expression is elevated in some malignancies; however, information is scarce regarding COX-2 contributions to the development of prostate cancer and its regulation by inflammatory cytokines.
Design, synthesis and biological evaluation of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy.
Evidence includes a direct relationship between COX-2 expression and cancer incidence in humans and animal models, increased tumorigenesis after genetic manipulation of COX-2, and significant anti-tumor properties of non-steroidal anti-inflammatory drugs in animal models and in some human cancers.
Expression of COX-2 and p53 proteins was examined by immunohistochemistry in paraffin-embedded cancer tissue blocks, and the relationship between COX-2 and/or p53 expression with clinicopathologic parameters was analyzed.