Antiproliferative effects of COX-2 inhibitor celecoxib on human breast cancer cell lines.

Abstract

The inducible COX-2 enzyme is over-expressed in human breast cancer and its over-expression generally correlates with angiogenesis, deregulation of apoptosis and worse prognosis. This observation may explain the beneficial effect of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors on breast cancer treatment. Here, we evaluated the antiproliferative activity of celecoxib, a selective COX-2 inhibitor, and its nitro-oxy derivative on human breast cancer cells characterized by low and high COX-2 expression, respectively. In ERα(+) MCF-7 cells celecoxib and its derivative induce a strong inhibition of cell growth, inhibition that is associated with the reduction of ERα expression and activation. These effects may be directly associated with ERK and Akt suppression and with PP2A and PTEN induction. In this cell line the drugs exert only weak effect on COX-2 level while they are able to reduce aromatase expression. On the contrary, in ERα(-) MDA-MB-231 cells, both drugs induce a marked inhibition of COX-2, inhibition that is associated with the reduction of aromatase expression and of cell proliferation. In both cell lines the effects of the drugs are associated with the suppression of cell invasion.

• Authors: Claudia Bocca, Francesca Bozzo, Andrea Bassignana, Antonella Miglietta
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 350 Issue 1-2 Pg. 59-70 (Apr 2011) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 21140284 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cyclooxygenase 2 Inhibitors
• Pyrazoles
• Sulfonamides
• Celecoxib

Topics

• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (pathology)
• Carcinoma (pathology)
• Celecoxib
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Drug Evaluation, Preclinical
• Female
• Humans
• MAP Kinase Signaling System (drug effects)
• Models, Biological
• Neoplasm Invasiveness
• Pyrazoles (pharmacology)
• Sulfonamides (pharmacology)