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 gamma (PPAR gamma) ligands inhibit cell proliferation and induce apoptosis in cancer cells. Here we wished to determine whether the PPAR gamma ligand induces apoptosis and cell cycle arrest of the MDA-MB-231 cell, an estrogen receptor alpha negative breast cancer cell line. The treatment of MDA-MB-231 cell with PPAR gamma ligands was shown to induce inhibition of cell growth in a dose-dependent manner as determined by MTT assay. Cell cycle analysis showed a G(1) 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 mu M, to 3.1-fold at 50 mu M and to 3.5-fold at 75 mu M. Moreover, troglitazone treatment, applied in a dose- dependent manner, caused a marked decrease in pRb, cyclin D-1, cyclin D-2, cyclin D-3, Cdk2, Cdk4 and Cdk6 expression as well as a significant increase in p21 and p27 expression. These results indicate that troglitazone causes growth inhibition, G(1) arrest and apoptotic death of MDA-MB-231 cells. (c) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.