8-11-14-eicosatrienoic-acid and Head-and-Neck-Neoplasms

It has recently been found that 5-lipoxygenase (5-LO) and cytochrome P450-2J2 (CYP2J2), molecules capable of arachidonic acid (AA) metabolism, might promote cancer cell viability through several mechanisms similar to those of cyclooxygenase-2 (COX-2). We found that not only COX-2 expression, but also the expression of 5-LO and CYP2J2 is up-regulated in head and neck squamous cell carcinoma (HNSCC) cell lines. From these observations, we hypothesized that AA metabolism by 5-LO and/or CYP2J2 may lower the efficacy of anti-cancer effect by COX-2 inhibition.. Although COX-2 was highly expressed in all cell lines tested, COX-2-specific inhibition showed little growth-inhibitory effect in some cell lines. Inhibition of COX-2 resulted in increased production of LTB(4) and 14-15-DHET/EET, metabolites of 5-LO and CYP2J2, respectively. Combined knock-down of COX-2 and 5-LO or CYP2J2 by siRNA results in a decrease in cell proliferation and VEGF production. Furthermore, these results are dependent on 5-LO and CYP2J2 expression in cells.. Therefore, combined inhibition of COX-2 and 5-LO or CYP2J2 may be one way to overcome low efficacy of single inhibition of COX-2 in cancer cells. In addition, combined therapies should be chosen based on the expression of members of other AA metabolism pathways.

Topics: 8,11,14-Eicosatrienoic Acid; Antineoplastic Agents; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Cell Line, Tumor; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dinoprostone; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Leukotriene B4; Plasmids; RNA, Small Interfering; Transfection; Vascular Endothelial Growth Factor A