Eicosanoid metabolism in squamous cell carcinoma cell lines derived from primary and metastatic head and neck cancer and its modulation by celecoxib

Dimethyl-Celecoxib (DMC), a derivative of celecoxib that lacks cyclooxygenase-2-Inhibitory function, potently mimics the anti-tumor effects of celecoxib on burkitt’s lymphoma in vitro and in vivo

“…31,32,70,71 This was true even for cancer cell lines with greatly varying levels of COX-2 expression, i.e., the amount of intracellular COX-2 enzyme did not appear to modulate the potency of celecoxib. 29,72 While the details of these differential sensitivities certainly deserve further investigation, these results further indicate that growth inhibition by celecoxib might be mediated by targets other than COX-2. In this regard, we envision that DMC presents a useful tool for the further exploration of these COX-2 independent effects.…”

Proteomic Profiling Identifies Cyclooxygenase-2-Independent Global Proteomic Changes by Celecoxib in Colorectal Cancer Cells

“…Second, treatment with celecoxib resulted in growth inhibition of xenografts of COX-2-deficient colorectal and prostate cancer cell lines in nude mice (8,14). Third, concentration of celecoxib needed for growth inhibition in vitro is several orders of magnitude higher than the concentration at which COX-2 is inhibited (15,16). And finally, derivatives of celecoxib devoid of the COX-2 inhibitory activity have recently been shown to mimic celecoxib by affecting processes such as cell cycle progression, apoptosis, neovascularization, growth inhibition in vitro, and tumor formation in vivo (17)(18)(19)(20).…”

Arachidonic Acid Metabolism and Its Implication on Head and Neck Cancer

“…It was shown that inhibition of COX-2 might lead to a shunt of AA metabolism towards the LT pathway in HNC. Suppressing PGE 2 levels by a COX-2 inhibitors, celecoxib, leads to an increase in the activity of 5-LOX, 12-LOX and 15-LOX-2 and results in the increase of their products, including, 5-HETE, 12-HETE and 15-HETE (Schroeder et al, 2004). A study in the mouse model of HNC, demonstrated an increase of LTB4 in tumor tissues in mice treated with PGE 2 .…”

“…Therefore, it is not surprised that LOX metabolites, including 5-HETE, 12-HETE, 15-HETE and 13-HODE were found in primary and metastatic HNSCC cells. However, there was no correlation between LOX isoforms and their metabolites in HNSCC cells (Schroeder et al, 2004). The level of LTB4, a metabolite of the 5-LOX pathway, was found to be higher in oral cancer lesions in human and hamsters (elHakim et al, 1990;Li et al, 2005).…”