[en] Malignant astrocytomas are among the most common brain tumours and few therapeutic options exist. It has recently been recognized that the ligand-activated nuclear receptor PPARgamma can regulate cellular proliferation and induce apoptosis in different malignant cells. We report the effect of three structurally different PPARgamma agonists inducing apoptosis in human (U87MG and A172) and rat (C6) glioma cells. The PPARgamma agonists ciglitazone, LY171 833 and prostaglandin-J2, but not the PPARalpha agonist WY14643, inhibited proliferation and induced cell death. PPARgamma agonist-induced cell death was characterized by DNA fragmentation and nuclear condensation, as well as inhibited by the synthetic receptor-antagonist bisphenol A diglycidyl ether (BADGE). In contrast, primary murine astrocytes were not affected by PPARgamma agonist treatment. The apoptotic death in the glioma cell lines treated with PPARgamma agonists was correlated with the transient up-regulation of Bax and Bad protein levels. Furthermore, inhibition of Bax expression by specific antisense oligonucleotides protected glioma cells against PPARgamma-mediated apoptosis, indicating an essential role of Bax in PPARgamma-induced apoptosis. However, PPARgamma agonists not only induced apoptosis but also caused redifferentiation as indicated by outgrowth of long processes and expression of the redifferentiation marker N-cadherin in response to PPARgamma agonists. Taken together, treatment of glioma cells with PPARgamma agonists may hold therapeutic potential for the treatment of gliomas.
Disciplines :
Neurology
Author, co-author :
Zander, Thomas; Department of Neurology, University Bonn, Germany
Kraus, Jürgen A; Department of Neurology, University Bonn, Germany
Grommes, Christian
Schlegel, Uwe; Department of Neurology, University Bonn, Germany
Feinstein, Douglas; Department of Neuroanesthesia Research, University of Illinois, Chicago, IL, United States
Klockgether, Thomas; Department of Neurology, University Bonn, Germany
Landreth, Gary; Department of Neuroscience, Case Western Reserve University, School of Medicine, Cleveland, United States
Koenigsknecht, Jessica; Department of Neuroanesthesia Research, University of Illinois, Chicago, IL, United States
HENEKA, Michael ; Department of Neurology, University Bonn, Germany ; Department of Neuroanesthesia Research, University of Illinois, Chicago, IL, United States ; Department of Neurology, University Bonn, 53105 Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARgamma.
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