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Received for publication October 25, 2004.
Revised January 18, 2005.
Accepted for publication January 19, 2005.
ligand GW7845 induces apoptosis and limits migration and
invasion of rat and human glioma cells
Despite new approaches, treatment options for malignant
gliomas are still limited, calling for further
development of therapeutic strategies. The peroxisome
proliferator-activated receptor gamma (PPAR
), a
member of the nuclear hormone receptor family, represents
a possible new target for neoplastic therapies. Synthetic
PPAR agonists were developed and are already in
clinical use for the treatment of type II diabetes, since
PPAR plays a crucial role in lipid metabolism and
regulation of insulin-sensitivity. Beyond these metabolic
effects, PPAR agonists exhibit antineoplastic
effects in various malignant tumor cells. Here, we
investigated the antineoplastic effects of the non-
thiazolidinedione tyrosine-based PPAR ligand 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 TUNEL staining and cleaved caspase-3
activation. Furthermore, GW7845 reduced proliferation of
C6 glioma cells as measured by Ki-67 immunreactivity.
There was also a reduction of migration and invasion,
assessed by Boyden-chamber and spheroid experiments.
Together, these data indicate that the PPAR agonist
GW7845 may be of potential use in treatment of malignant
gliomas.
Key words:
GW7845, PPAR
, apoptosis, glioma, invasion, non-thiazolidinedione
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