SURAMIN INHIBITS GLIOMA CELL-PROLIFERATION IN-VITRO AND IN THE BRAIN

Citation
S. Takano et al., SURAMIN INHIBITS GLIOMA CELL-PROLIFERATION IN-VITRO AND IN THE BRAIN, Journal of neuro-oncology, 21(3), 1994, pp. 189-201
Citations number
47
Categorie Soggetti
Neurosciences,Oncology
Journal title
ISSN journal
0167594X
Volume
21
Issue
3
Year of publication
1994
Pages
189 - 201
Database
ISI
SICI code
0167-594X(1994)21:3<189:SIGCIA>2.0.ZU;2-O
Abstract
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.