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Growth Inhibition and Apoptosis Induced in Human Leiomyoma Cells by Treatment With the PPAR Gamma Ligand Ciglitizone

Growth Inhibition and Apoptosis Induced in Human Leiomyoma Cells by Treatment With the PPAR Gamma Ligand Ciglitizone

Dong-Ho Nam, Sabarish Ramachandran, Dae-Kyu Song, Kun-Young Kwon, Dong-Seok Jeon, So-Jin Shin, Sang-Hoon Kwon, Soon-Do Cha, Insoo Bae, Chi-Heum Cho

Mol Hum Reprod. 2007 Nov;13(11):829-36.

PMID: 17893092

Abstract:

The nuclear receptors PPARs (peroxisome proliferator-activated receptors) are transcription factors that play important roles in multiple disease conditions. The activation of PPARs by specific ligands is associated with growth suppression of several different types of human cancer, but the molecular mechanism responsible for this growth suppressive effect remains elusive. The aim of this study was to determine the distribution of PPARgamma protein/mRNA expression in uterine leiomyomas and to identify the PPARgamma induced signaling pathways responsible for the growth inhibition induced by treatment with ciglitizone, a synthetic ligand of PPARgamma, in view of identifying targets that could possibly affect the viability and proliferation of uterine leiomyoma cells. Dose-response studies on proliferation found that uterine leiomyoma was more sensitive to inhibition by ciglitizone treatments than normal myometrium. We also found that ciglitizone significantly stimulated gene expression driven by a PPAR-responsive element in cultured leiomyoma cells and reduced the survival of leiomyoma cells relative to the control cells. The reduced survival of ciglitizone treated leiomyoma cells resulted from a mechanism that involved the Fas receptor-mediated apoptosis signaling cascade. These results suggest that uterine leiomyomas growth and differentiation might be modulated through PPARgamma receptors and that PPARgamma ligands may be of potential use for uterine leiomyoma treatment.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP74772773-B	Ciglitizone		74772-77-3	Price

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