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KMID : 1134120060090040293
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Journal of Breast Cancer
2006 Volume.9 No. 4 p.293 ~ p.300
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Peroxisome proliferator-activated receptor gamma activator inhibits cell growth of MDA-MB-231 breast cancer cells through induction of apoptosis
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Jo Eun-Jeong
Youn Hyun-Jo
Jung Sung-Hoo
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Abstract
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Purpose: Peroxisome proliferator-activated receptor gamma (PPAR?) has become a potential target for the prevention and treatment of human cancers. PPAR? ligands inhibit cell proliferation of estrogen receptor?(ER?)-positive breast cancer cells. However, it has recently been shown that ER?-negatively inhibits PPAR? signaling in breast cancer cells, indicating that PPAR? ligand may be more useful for treating ER?-negative breast cancer cells compared to ER?-positive breast cancer cells. In this study, we attempted to elucidate the role of PPARg in ER?-negative breast cancer cells.
Methods: The effect of PPAR? ligand 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 PPAR? ligand 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 PPAR? ligand, 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 50?M 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?-negative MDA-MB-231 breast cancer cells. Collectively, this paper shows that PPAR? ligand is an important player as a member of the chemotherapeutic candidates for treating ER?-negative breast cancer. (J Breast Cancer 2006;9: 293-300)
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KEYWORD
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ER-negative MDA-MB-231 breast cancer cells, PPAR?, Apoptosis, Cell
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