Despite new approaches, treatment options for
malignant gliomas are still limited, calling for further development of therapeutic strategies. The
peroxisome proliferator-activated receptor (
PPAR)gamma, a member of the
nuclear hormone receptor family, represents a possible new target for neoplastic
therapies. Synthetic
PPARgamma agonists were developed and are already in clinical use for the treatment of type II diabetes, since
PPARgamma plays a crucial role in lipid metabolism and regulation of
insulin sensitivity. Beyond these metabolic effects,
PPARgamma agonists exhibit
antineoplastic effects in various malignant
tumor cells. Here, we investigated the
antineoplastic effects of the nonthiazolidinedione
tyrosine-based
PPARgamma 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
PPARgamma agonist
GW7845 may be of potential use in treatment of
malignant gliomas.