Suramin Affects DNA Synthesis in HeLa Cells by Inhibition of DNA Polymerases

Hitesh K. Jindal, Christopher W. Anderson, Randall G. Davis, Jamboor K. Vishwanatha

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43 Scopus citations

Abstract

Suramin, a polysulfonated naphthylurea widely used in the treatment of trypanosomiasis and onchocerciasis, is currently being investigated as an antitumor agent for the treatment of advanced cancer. Suramin exerts a wide variety of biological effects. We have shown that suramin inhibits cell proliferation and DNA synthesis in cultured HeLa cells. The replication in vitro of SV40 DNA is completely abolished by 40 μm suramin. The inhibition of DNA replication is due to inhibition of DNA polymerases α and δ, the replicative enzymes in eukaryotic cells. DNA polymerase a is sensitive to lower concentrations of suramin [concentration to achieve 50% inhibition (IC50) of 8 μm] than is DNA polymerase δ (IC50 36 μm), whereas DNA polymerase β is relatively insensitive to the drug (IC50 of 90 μm). Suramin inhibits other replicative DNA polymerases such as Escherichia coli polymerase I (Klenow fragment) and Thermus aquaticus polymerase. Suramin is noncompetitive with both substrate deoxyribo-nucleotides and template-primers with respect to DNA polymerase inhibition. Much lower concentrations (8-30 μm) of the drug are required for 50% inhibition of DNA polymerases than for 50% inhibition of other enzymes such as protein kinase C and reverse transcriptase. These results show an important biological effect of this drug and indicate the need for more studies before its clinical use as an antitumor agent.

Original languageEnglish
Pages (from-to)7754-7757
Number of pages4
JournalCancer Research
Volume50
Issue number24
StatePublished - 15 Dec 1990

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    Jindal, H. K., Anderson, C. W., Davis, R. G., & Vishwanatha, J. K. (1990). Suramin Affects DNA Synthesis in HeLa Cells by Inhibition of DNA Polymerases. Cancer Research, 50(24), 7754-7757.