Induction of cell cycle arrest and apoptosis in breast cancer cells by troglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligand.

Abstract

Abstract Abstract #5034 Background: Peroxisome proliferator-activated receptor-gamma(PPAR-γ) ligands inhibit cell proliferation and induce apoptosis in cancer cells. And, it is reported that PPAR-γ ligands could serve as negative regulators of breast cancer development and progression, but their mechanism is still unknown. Here we wished to determine whether the PPAR-γ ligand induces cell cycle arrest and apoptosis of MDA-MB-231(ERα-negative) and MCF-7(ERα-positive) breast cancer cell.
 Methods: The effect of PPAR-γ ligands on the cell viability of breast cancer cells was determined using mitochondrial tetrazolium(MTT) assay. The cell cycle distribution and apoptosis induction were evaluated by using the flow cytometry. The expression of apoptosis-related proteins were measured with Western blot analysis. Statistical analysis was performed using Student's t test, and p<0.05 was considered significant.
 Results: The treatment of MDA-MB-231 cell with PPAR-γ ligand, troglitazone was shown to induce cell cycle G1 arrest and induction of apoptosis. Moreover, troglitazone treatment, applied in a dose-dependent manner, caused a marked decrease in phosphorylated retinoblastoma(pRb), cyclin D1, D2, D3, cyclin dependent kinase(Cdk) 2, 4, and 6 expression as well as a significant increase in Cdk inhibitor, p21 and p27. Troglitazone showed antiproliferative effect on MCF-7 cell with tamoxifen, respectively and synergically. Troglitazone and tamoxifen could induce G1 arrest and apoptosis of MCF-7 cell, through upregulation of Bax and downregulation of Bcl-2 and cyclin D1.
 Conclusion: PPAR-γ ligand, troglitazone induces cell cycle arrest and apoptosis of MDA-MB-231 cell and increases the sensitivity of anti-hormonal therapy in MCF-7 cell. These results suggest that troglitazone has anticancer effect on both ERα-negative and positive breast cancer cells. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5034.