Suramin is a novel anticancer agent that blocks the binding of growth
factors, including basic fibroblast growth factor (bFGF), to their rec
eptors. Prior studies showed human and experimental gliomas to upregul
ate and respond to autocrine stimulation by bFGF, the antiproliferativ
e effects of suramin were therefore studied on glioma cell turnover in
vitro and in the brain. Suramin inhibited the growth of rat (C6, 9L)
and human (U-118, U-138, A-172, T98G) glioma cell lines in a dose-depe
ndent manner. Suramin significantly reduced the bromodeoxyuridine (BUd
R) labeling index of cultured glioma cells at 250 mu g/ml, P < 0.0001.
DNA flow cytometry revealed a significant decrease in the percentage
of suramin-treated glioma cells in S-phase, P < 0.01. Using intracereb
ral rat C6 glioma model in vivo, suramin, 10-60 mg/kg, i.p., produced
a dose-dependent reduction of BUdR labeling in both the glioma and end
othelial cell subpopulations. Suramin, 200 mg/kg i.v., however, led to
intratumoral hemorrhages that reduced survival. Electron microscopy r
evealed membranous inclusion bodies in the cytoplasm of C6 glioma and
endothelial cells, an indication of excess glycosaminoglycans. Moreove
r, 46% of endothelial cells within the C6 glioma tumor treated with su
ramin, 60 mg/kg, i.p., developed membrane blebs. Suramin, in clinicall
y relevant doses, significantly inhibits glioma cell growth and cytoki
netics. The risk of intratumoral hemorrhage, possibly related to injur
y of endothelial cells or the accumulation of anticoagulant glycosamin
oglycans, constitutes a major side effect and caution should be exerci
sed in consideration of clinical application for intracerebral tumors.