Apoptotic Effect of the Cyclooxygenase-2 Inhibitor Celecoxib on Human Breast Cancer MDA-MB 468 Cells / 한국유방암학회지
Journal of Breast Cancer
;
: 193-199, 2006.
Article
in Korean
| WPRIM
| ID: wpr-118414
ABSTRACT
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Breast
/
Breast Neoplasms
/
DNA
/
Signal Transduction
/
Cell Survival
/
Prostaglandins
/
Blotting, Western
/
Cytokines
/
NF-kappa B
Limits:
Humans
Language:
Korean
Journal:
Journal of Breast Cancer
Year:
2006
Type:
Article
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