Inhibition of cyclooxygenase-2 and activation of peroxisome proliferator-activated receptor-γ synergistically induces apoptosis and inhibits growth of human breast cancer cells
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- Published online on: June 1, 2003 https://doi.org/10.3892/ijmm.11.6.733
- Pages: 733-736
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Abstract
Cyclooxygenase-2 (COX-2) expression and peroxisome proliferator-activated receptor-γ (PPARγ) inactivation are linked to increased risk of human breast cancer. This study examines the effect of simultaneous targeting of COX-2 and PPARγ on the proliferation of human breast cancer cells and on the expression of Bcl-2, BAX, and caspases-3 and -9, modulators of apoptotic cell death. Treatment of MDA-MB-231 breast cancer cells with NS-398 (a COX-2 inhibitor) or ciglitazone (CGZ, a PPARγ-ligand) significantly inhibited cell proliferation and markedly increased apoptotic rates. These effects were accompanied by upregulation of BAX and caspases-3 and -9 mRNA expression and downregulation of Bcl-2. Compared to the influence of separate treatments, simultaneous treatment with NS-398 and CGZ synergistically inhibited cell proliferation and induced apoptotic cell death. In conclusion, combinational targeting of COX-2 and PPARγ can inhibit the growth of human breast cancer cells and induce apoptosis to an extent more suprior to that produced by targeting each molecule alone. COX-2 and PPARγ can be promising molecular targets for combinational chemoprevention or treatment of breast cancer.