Suramin affects DNA synthesis in HeLa cells by inhibition of DNA polymerases.
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 microM suramin. The inhibition of DNA replication is due to inhibition of DNA polymerases alpha and delta, the replicative enzymes in eukaryotic cells. DNA polymerase alpha is sensitive to lower concentrations of suramin [concentration to achieve 50% inhibition (IC50) of 8 microM] than is DNA polymerase delta (IC50 36 microM), whereas DNA polymerase beta is relatively insensitive to the drug (IC50 of 90 microM). Suramin inhibits other replicative DNA polymerases such as Escherichia coli polymerase I (Klenow fragment) and Thermus aquaticus polymerase. Suramin is noncompetitive with both substrate deoxyribonucleotides and template-primers with respect to DNA polymerase inhibition. Much lower concentrations (8-30 microM) 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.
Jindal
H K
HK
Department of Biochemistry, University of Nebraska Medical Center, Omaha 68198-4525.
Anderson
C W
CW
Davis
R G
RG
Vishwanatha
J K
JK
D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis* / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D019384:Nucleic Acid Synthesis Inhibitors; D013539:Simian virus 40 / Q000235:genetics; D013498:Suramin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D004273:DNA, Neoplasm; D004279:DNA, Viral; D019384:Nucleic Acid Synthesis Inhibitors; D013498:Suramin; D004257:DNA Polymerase II; D013936:Thymidine