NDLI: Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells.

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Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells.

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Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Jacquemin-sablon, A. Larsen, A. K. Couprie, J. Lelievre, S. Markovits, J. Bojanowski, K.
Description	Author Affiliation: Bojanowski K ( Laboratoire de Pharmacologie Moléculaire, Institut Gustave Roussy, Villejuif, France.);
Abstract	The antitrypanosomal and antifiliarial drug suramin is currently under investigation for treatment of advanced malignancies including prostatic cancer, adrenocortical cancer, and some lymphomas and sarcomas. Here we show that suramin is a potent inhibitor of the nuclear enzyme DNA topoisomerase II. Suramin inhibited purified yeast topoisomerase II with an IC50 of about 5 microM, as measured by decatenation or relaxation assays. Suramin did not stabilize the covalent DNA-topoisomerase II reaction intermediate ('cleavable complex'), whereas other inhibitors of this enzyme, such as amsacrine, etoposide, and the ellipticines, are known to stabilize the intermediate. In contrast, the presence of suramin strongly inhibited the cleavable-complex formation induced by amsacrine or etoposide. Accumulation of the endogenous cleavable complex was also inhibited. Suramin entered the nucleus of DC-3F Chinese hamster fibrosarcoma cells exposed to radiolabeled suramin for 24 hr as shown by both optic and electron microscopy. The suramin present in the nucleus seemed to interact with topoisomerase II, since suramin reduced the number of amsacrine-induced protein-associated DNA strand breaks in DC-3F cells and protected these cells from the cytotoxic action of amsacrine. Cells resistant to 9-hydroxyellipticine, which have been shown to have an altered topoisomerase II activity, are about 7-fold more resistant to suramin than the sensitive parental cells as shown by 72-hr growth inhibition assay. Our results suggest that DNA topoisomerase II is a target of suramin action and that this action may play a role in the cytotoxic activity of suramin.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	7
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Suramin Pharmacology Topoisomerase II Inhibitors Amsacrine Animals Cell Compartmentation Cell Division Drug Effects Cricetinae Cricetulus DNA Damage Fibrosarcoma In Vitro Techniques Nucleic Acid Denaturation Saccharomyces Cerevisiae Enzymology Tumor Cells, Cultured Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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