Induction of G₁ phase arrest and apoptosis in MDA-MB-231 breast cancer cells by troglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand

Peroxisome proliferator-activated receptor γ (PPARγ) ligands inhibit cell proliferation and induce apoptosis in cancer cells. Here we wished to determine whether the PPARγ ligand induces apoptosis and cell cycle arrest of the MDA-MB-231 cell, an estrogen receptor α negative breast cancer cell line. The treatment of MDA-MB-231 cell with PPARγ ligands was shown to induce inhibition of cell growth in a dose-dependent manner as determined by MTT assay. Cell cycle analysis showed a G₁ arrest in MDA-MB-231 cells exposed to troglitazone. An apoptotic effect by troglitazone demonstrated that apoptotic cells elevated by 2.5-fold from the control level at 10 μM, to 3.1-fold at 50 μM and to 3.5-fold at 75 μM. Moreover, troglitazone treatment, applied in a dose-dependent manner, caused a marked decrease in pRb, cyclin D₁, cyclin D₂, cyclin D₃, Cdk2, Cdk4 and Cdk6 expression as well as a significant increase in p21 and p27 expression. These results indicate that troglitazone causes growth inhibition, G₁ arrest and apoptotic death of MDA-MB-231 cells.