Suramin inhibits glioma cell proliferationin vitro and in the brain

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

DOI: 10.1007/BF01063768

关键词: Flow cytometryBiologyReceptorCancer researchBasic fibroblast growth factorSuraminGliomaImmunologyIn vivoAutocrine signallingEndothelial stem cellOncologyNeurologyClinical neurology

摘要: Suramin is a novel anticancer agent that blocks the binding of growth factors, including basic fibroblast factor (bFGF), to their receptors. Prior studies showed human and experimental gliomas upregulate respond autocrine stimulation by bFGF, antiproliferative effects suramin were therefore studied on glioma cell turnoverin vitro in brain. inhibited rat (C6,9L) (U-118, U-138, A-172, T98G) lines dose-dependent manner. significantly reduced bromodeoxyuridine (BUdR) labeling index cultured cells at 250 µg/ml, P < 0.0001. DNA flow cytometry revealed significant decrease percentage suramin-treated S-phase, 0.01. Using intracerebral C6 modelin vivo, suramin, 10–60 mg/kg, i.p., produced reduction BUdR both endothelial subpopulations. Suramin, 200 mg/kg i.V., however, led intratumoral hemorrhages survival. Electron microscopy membranous inclusion bodies cytoplasm cells, an indication excess glycosaminoglycans. Moreover, 46% within tumor treated with 60 developed membrane blebs. clinically relevant doses, inhibits cytokinetics. The risk hemorrhage, possibly related injury or accumulation anticoagulant glycosaminoglycans, constitutes major side effect caution should be exercised consideration clinical application for tumors.

参考文章(43)
D Zagzag, F Robert, S Brem, Neovascularization and tumor growth in the rabbit brain. A model for experimental studies of angiogenesis and the blood-brain barrier. American Journal of Pathology. ,vol. 131, pp. 361- 372 ,(1988)
D. Zagzag, S. Gately, S. E. Brien, A. M. C. Tsanaclis, M.-P. Elkouby, S. S. Brem, Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor. American Journal of Pathology. ,vol. 137, pp. 1121- 1142 ,(1990)
Nobuaki Okumura, Kouichi Takimoto, Masato Okada, Hachiro Nakagawa, C6 glioma cells produce basic fibroblast growth factor that can stimulate their own proliferation. Journal of Biochemistry. ,vol. 106, pp. 904- 909 ,(1989) , 10.1093/OXFORDJOURNALS.JBCHEM.A122950
Jamboor K. Vishwanatha, Hitesh K. Jindal, Randall G. Davis, Christopher W. Anderson, Suramin Affects DNA Synthesis in HeLa Cells by Inhibition of DNA Polymerases Cancer Research. ,vol. 50, pp. 7754- 7757 ,(1990)
A. Gagliardi, H. Hadd, D. C. Collins, Inhibition of angiogenesis by suramin. Cancer Research. ,vol. 52, pp. 5073- 5075 ,(1992)
David M. Nanus, Victor Reuter, Dean F. Bajorin, Paul O'Moore, Carl Louison, Jacqueline Iversen, Anthony P. Albino, Robert J. Motzer, William P. Tong, George J. Bosl, Howard I. Scher, Phase II Trial of Suramin in Patients with Advanced Renal Cell Carcinoma: Treatment Results, Pharmacokinetics, and Tumor Growth Factor Expression Cancer Research. ,vol. 52, pp. 5775- 5779 ,(1992)
Howard I. Scher, Tracy Curley, Alan Forrest, Jacqueline M. Iversen, Merrill J. Egorin, William Tong, Duncan I. Jodrell, Use of adaptive control with feedback to individualize suramin dosing. Cancer Research. ,vol. 52, pp. 64- 70 ,(1992)
David E. Burstein, Daniel B. Rifkin, David Zagzag, Douglas C. Miller, Yasufumi Sato, Immunohistochemical Localization of Basic Fibroblast Growth Factor in Astrocytomas Cancer Research. ,vol. 50, pp. 7393- 7398 ,(1990)
N Vaisman, D Gospodarowicz, G Neufeld, Characterization of the receptors for vascular endothelial growth factor. Journal of Biological Chemistry. ,vol. 265, pp. 19461- 19466 ,(1990) , 10.1016/S0021-9258(17)45395-6