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Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARγ
Author(s) -
Zander Thomas,
Kraus Jürgen A.,
Grommes Christian,
Schlegel Uwe,
Feinstein Douglas,
Klockgether Thomas,
Landreth Gary,
Koenigsknecht Jessica,
Heneka Michael T.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00899.x
Subject(s) - ciglitazone , apoptosis , peroxisome proliferator activated receptor , agonist , glioma , receptor , biology , programmed cell death , nuclear receptor , cancer research , microbiology and biotechnology , chemistry , biochemistry , transcription factor , gene
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 PPARγ can regulate cellular proliferation and induce apoptosis in different malignant cells. We report the effect of three structurally different PPARγ agonists inducing apoptosis in human (U87MG and A172) and rat (C6) glioma cells. The PPARγ agonists ciglitazone, LY171 833 and prostaglandin‐J2, but not the PPARα agonist WY14643, inhibited proliferation and induced cell death. PPARγ 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 PPARγ agonist treatment. The apoptotic death in the glioma cell lines treated with PPARγ 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 PPARγ‐mediated apoptosis, indicating an essential role of Bax in PPARγ‐induced apoptosis. However, PPARγ 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 PPARγ agonists. Taken together, treatment of glioma cells with PPARγ agonists may hold therapeutic potential for the treatment of gliomas.