RESUMEN
Purpose: Cyclooxygenase (COX) is an enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The inducible form, COX-2, is induced by such proinflammatory and mitogenic stimuli as cytokines and growth factors, and it's expressed in inflamed tissues as well as neoplastic tissues. In addition, COX-2 inhibitors have been tried as chemopreventive agents in tumors. In order to elucidate the mechanisms of COX-2 inhibitors in human breast cancer, the effects of celecoxib, a well-known selective COX-2 inhibitor, on cell death in human breast MDA-MB-468 cancer cells were investigated. METHODS: Cell viability assay, PI staining, DNA fragmentation assay and western blot analysis were performed after treatment with celecoxib. RESULTS: Cell survival, as measured by MTT assay, was decreased by the treatment with celecoxib in a dose-dependent manner (IC50=50 micrometer). The sub-G1 fractions, analyzed by flow cytometry, and the DNA fragmentations were increased in a dose-dependent manner, suggesting that celecoxib induces apoptotic cell death in MDA-MB-468 cells. Celecoxib resulted in a decrease in the levels of COX-2 protein in a time-depended and dose-dependent manner. To investigate the mechanisms of celecoxib-induced apotosis, the activation of MAPK, NF-kB and Akt was analyzed by Western blotting. The treatment with celecoxib induces an increase in JNK phosphorylation and IkB degradation and a decrease in Akt phosphorylation. CONCLUSION: These results suggest that celecoxib-induced apoptosis is mediated through the signal transduction pathways associated with JNK, Akt and NF-kB in human breast cancer MDA-MB-468 cells.