J Breast Cancer.  2006 Sep;9(3):193-199. 10.4048/jbc.2006.9.3.193.

Apoptotic Effect of the Cyclooxygenase-2 Inhibitor Celecoxib on Human Breast Cancer MDA-MB 468 Cells

• Cha Y
• Ko HS
• Kim H
• Kim JR
• Kim JH

• KMID: 2286649
• DOI: http://doi.org/10.4048/jbc.2006.9.3.193

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.

Keyword

Apoptosis; Breast cancer; Celecoxib

MeSH Terms

Apoptosis
Arachidonic Acid
Blotting, Western
Breast Neoplasms*
Breast*
Celecoxib
Cell Death
Cell Survival
Cyclooxygenase 2 Inhibitors
Cyclooxygenase 2*
Cytokines
DNA
DNA Fragmentation
Flow Cytometry
Humans*
Intercellular Signaling Peptides and Proteins
NF-kappa B
Phosphorylation
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Signal Transduction
Arachidonic Acid
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cytokines
DNA
Intercellular Signaling Peptides and Proteins
NF-kappa B
Prostaglandin-Endoperoxide Synthases
Prostaglandins