Differential anti-proliferative actions of peroxisome proliferator-activated receptor-γ agonists in MCF-7 breast cancer cells

2006 ◽  
Vol 72 (5) ◽  
pp. 530-540 ◽  
Author(s):  
Ki Young Kim ◽  
Sung Soo Kim ◽  
Hyae Gyeong Cheon
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mcf 7

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.

The peroxisome proliferator-activated receptor γ is an inhibitor of ErbBs activity in human breast cancer cells

2001 ◽  
Vol 114 (22) ◽  
pp. 4117-4126 ◽  
Author(s):  
Miguel Pignatelli ◽  
Marta Cortés-Canteli ◽  
Cary Lai ◽  
Angel Santos ◽  
Ana Perez-Castillo
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tyrosine Kinases ◽  
Breast Cancer Cells ◽  
Erbb Receptors ◽  
Breast Cancer Cell Lines ◽  
Peroxisome Proliferator ◽  
Receptor Field ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mcf 7

One of the most interesting recent developments in the nuclear receptor field has been the identification of natural and synthetic agonists of the peroxisome proliferator-activated receptor (PPAR) family, coupled with a growing recognition that the γ isoform (PPARγ) affects pathways important in a variety of human diseases. Here we show that the activation of PPARγ through the 15-deoxy-Δ-12,14-prostaglandin J2 (PG-J2) ligand causes a dramatic inhibition of ErbB-2 and ErbB-3 tyrosine phosphorylation caused by neuregulin 1 (NRG1) and neuregulin 2 (NRG2) in MCF-7 cells. This effect is accompanied by a very efficient blocking of ErbBs effects upon proliferation, differentiation and cell death in these cells. Preincubation of MCF-7 cells with PG-J2 before addition of NRG1 and NRG2 had a dramatic growth-suppressive effect accompanied by accumulation of cells in the G0/G1 compartment of the cell cycle, and a marked increase in apoptosis. NRG1 and NRG2 induce G1 progression, which was associated with stimulation of the phosphatidylinositol-3 kinase (PI 3-K) pathway, whereas survival was dependent on ERK1/ERK2 activation. Both pathways were inhibited by PG-J2. Furthermore, PG-J2 can abolish the NRG1 and NRG2-induced increase in anchorage-independent growth of these cells. PG-J2 also blocks phosphorylation of other receptor tyrosine kinases, such as IGF-IR, in MCF-7 cells, and suppress proliferation of other breast cancer cell lines. In summary, our data show a specific inhibitory action of PG-J2 on the activity of the ErbB receptors in breast cancer cells.

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.

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