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Suramin inhibits glioma cell proliferationin vitro and in the brain

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Summary

Suramin is a novel anticancer agent that blocks the binding of growth factors, including basic fibroblast growth factor (bFGF), to their receptors. Prior studies showed human and experimental gliomas to upregulate and respond to autocrine stimulation by bFGF, the antiproliferative effects of suramin were therefore studied on glioma cell turnoverin 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-dependent manner. Suramin significantly reduced the bromodeoxyuridine (BUdR) labeling index of cultured glioma cells at 250 µg/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 intracerebral rat C6 glioma modelin vivo, suramin, 10–60 mg/kg, i.p., produced a dose-dependent reduction of BUdR labeling in both the glioma and endothelial cell subpopulations. Suramin, 200 mg/kg i.V., however, led to intratumoral hemorrhages that reduced survival. Electron microscopy revealed membranous inclusion bodies in the cytoplasm of C6 glioma and endothelial cells, an indication of excess glycosaminoglycans. Moreover, 46% of endothelial cells within the C6 glioma tumor treated with suramin, 60 mg/kg, i.p., developed membrane blebs. Suramin, in clinically relevant doses, significantly inhibits glioma cell growth and cytokinetics. The risk of intratumoral hemorrhage, possibly related to injury of endothelial cells or the accumulation of anticoagulant glycosaminoglycans, constitutes a major side effect and caution should be exercised in consideration of clinical application for intracerebral tumors.

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Authors and Affiliations

  1. Division of Neurological Surgery, Northwestern Memorial Hospital and School of Medicine, Chicago, Illinois, USA

    Shingo Takano, Stephen Gately, Herbert Engelhard, Ana Maria C. Tsanaclis & Steven Brem

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  1. Shingo Takano
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  2. Stephen Gately
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  3. Herbert Engelhard
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  4. Ana Maria C. Tsanaclis
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  5. Steven Brem
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Takano, S., Gately, S., Engelhard, H. et al. Suramin inhibits glioma cell proliferationin vitro and in the brain. J Neuro-Oncol 21, 189–201 (1994). https://doi.org/10.1007/BF01063768

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