Peroxisome proliferator-activated receptor gamma activator inhibits cell growth of MDA-MB-231 breast cancer cells through induction of apoptosis

Abstract

Purpose: Peroxisome proliferator-activated receptor gamma (PPARγ) has become a potential target for the prevention and treatment of human cancers. PPARγligands inhibit cell proliferation of estrogen receptorα(ERα)-positive breast cancer cells. However, it has recently been shown that ERα-negatively inhibits PPARγsignaling in breast cancer cells, indicating that PPARγligand may be more useful for treating ERα-negative breast cancer cells compared to ERα-positive breast cancer cells. In this study, we attempted to elucidate the role of PPARg in ERα-negative breast cancer cells. Methods: The effect of PPARγligand on the growth of MDA-MB-231 cells was measured by MTT assay and flow cytometric analysis. TUNEL staining and Hoechst 33342 fluorescent staining were used to observe the effects of PPARγligand on cell apoptosis. The regulatory proteins of the cell cycle were measured by Western blot. Results: The treatment of MDA-MB-231 human breast cancer cells with the PPARγligand, trgoglitazone, was shown to induce inhibition of cell growth in a dose-dependent manner. Cell cycle analysis showed a G1 arrest in MDA-MB-231 cells exposed to troglitazone. The apoptotic effect by troglitazone demonstrated that apoptotic cells were elevated from 2.5-fold of the control level at 10 mM, to 3.1-fold at 50μM and to 3.5-fold at 75 mM of troglitazone. Moreover, troglitazone treatment dose-dependently caused a marked decrease in the pRb, cyclin D1, cyclin D2, cyclin D3, cdk2, Cdk4 and Cdk6 expressions and there was a significant increase in the p21 and p27 expressions. Conclusion: These results indicate that trgoglitazone induces cell-cycle G1 arrest and apoptosis in ER α-negative MDA-MB-231 breast cancer cells. Collectively, this paper shows that PPARγligand is an important player as a member of the chemotherapeutic candidates for treating ERα-negative breast cancer. (J Breast Cancer 2006;9: 293-300)