Peroxisome Proliferator-Activated Receptor γ-Independent Ablation of Cyclin D1 by Thiazolidinediones and Their Derivatives in Breast Cancer Cells

2005 ◽  
Vol 67 (4) ◽  
pp. 1342-1348 ◽  
Author(s):  
Jui-Wen Huang ◽  
Chung-Wai Shiau ◽  
Ya-Ting Yang ◽  
Samuel K. Kulp ◽  
Kuen-Feng Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Synergistic Antiproliferative Effects of Combinedγ-Tocotrienol and PPARγAntagonist Treatment Are Mediated through PPARγ-Independent Mechanisms in Breast Cancer Cells

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Abhita Malaviya ◽  
Paul W. Sylvester
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Combined Treatment ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Antiproliferative Effects ◽  
Natural Ligand ◽  
Anticancer Effects ◽  
Cox 2

Previous findings showed that the anticancer effects of combinedγ-tocotrienol and peroxisome proliferator activated receptorγ(PPARγ) antagonist treatment caused a large reduction in PPARγexpression. However, other studies suggest that the antiproliferative effects ofγ-tocotrienol and/or PPARγantagonists are mediated, at least in part, through PPARγ-independent mechanism(s). Studies were conducted to characterize the role of PPARγin mediating the effects of combined treatment ofγ-tocotrienol with PPARγagonists or antagonists on the growth of PPARγnegative +SA mammary cells and PPARγ-positive and PPARγ-silenced MCF-7 and MDA-MB-231 breast cancer cells. Combined treatment ofγ-tocotrienol with PPARγantagonist decreased, while combined treatment ofγ-tocotrienol with PPARγagonist increased, growth of all cancer cells. However, treatment with high doses of 15d-PGJ2, an endogenous natural ligand for PPARγ, had no effect on cancer cell growth. Western blot and qRT-PCR studies showed that the growth inhibitory effects of combinedγ-tocotrienol and PPARγantagonist treatment decreased cyclooxygenase (COX-2), prostaglandin synthase (PGDS), and prostaglandin D2(PGD2) synthesis. In conclusion, the anticancer effects of combinedγ-tocotrienol and PPARγantagonists treatment in PPARγnegative/silenced breast cancer cells are mediated through PPARγ-independent mechanisms that are associated with a downregulation in COX-2, PGDS, and PGD2synthesis.

Effect of a synthetic peroxisome proliferator-activated receptor-gamma (PPARγ) ligand on breast cancer cells

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14638-e14638
Author(s):  
H. Youn ◽  
B. Lee ◽  
S. Jung
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Cycle Arrest ◽  
Mcf 7 ◽  
Positive Breast Cancer

e14638 Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) ligands have been identified as a potential source of therapy for human cancers. 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. The purpose of this study was 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. 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. Conclusions: 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. No significant financial relationships to disclose.

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