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KMID : 1134120060090030193
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Journal of Breast Cancer
2006 Volume.9 No. 3 p.193 ~ p.199
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Apoptotic Effect of the Cyclooxygenase-2 Inhibitor Celecoxib on Human Breast Cancer MDA-MB 468 Cells
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Cha Young
Ko Hyun-Sook
Kim Hoon
Kim Jae-Ryong
Kim Jung-Hye
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Abstract
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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 ?M). 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. (J Breast Cancer 2006;9: 193-199)
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KEYWORD
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Apoptosis, Breast cancer, Celecoxib
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