PT  - JOURNAL ARTICLE
AU  - Christian Grommes
AU  - Gary E. Landreth
AU  - Uwe Schlegel
AU  - Michael T. Heneka
TI  - The Nonthiazolidinedione Tyrosine-Based Peroxisome Proliferator-Activated Receptor γ Ligand GW7845 Induces Apoptosis and Limits Migration and Invasion of Rat and Human Glioma Cells
AID  - 10.1124/jpet.104.078972
DP  - 2005 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 806--813
VI  - 313
IP  - 2
4099  - http://jpet.aspetjournals.org/content/313/2/806.short
4100  - http://jpet.aspetjournals.org/content/313/2/806.full
SO  - J Pharmacol Exp Ther2005 May 01; 313
AB  - Despite new approaches, treatment options for malignant gliomas are still limited, calling for further development of therapeutic strategies. The peroxisome proliferator-activated receptor (PPAR)γ, a member of the nuclear hormone receptor family, represents a possible new target for neoplastic therapies. Synthetic PPARγ agonists were developed and are already in clinical use for the treatment of type II diabetes, since PPARγ plays a crucial role in lipid metabolism and regulation of insulin sensitivity. Beyond these metabolic effects, PPARγ agonists exhibit antineoplastic effects in various malignant tumor cells. Here, we investigated the antineoplastic effects of the nonthiazolidinedione tyrosine-based PPARγ ligand (S)-2-(1-carboxy-2-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}ethylamino)benzoic acid methyl ester (GW7845) in rat and human glioma cells. GW7845 reduced cellular viability of rat C6 glioma and human glioma cells in a time-dependent manner. Analysis of GW7845-treated tumor cells revealed induction of apoptotic cell death as determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and cleaved caspase-3 activation. Furthermore, GW7845 reduced proliferation of C6 glioma cells as measured by Ki-67 immunore-activity. There was also a reduction of migration and invasion, assessed by Boyden chamber and spheroid experiments. Together, these data indicate that the PPARγ agonist GW7845 may be of potential use in treatment of malignant gliomas. The American Society for Pharmacology and Experimental Therapeutics