Suramin is a prototype of a new class of anticancer drugs. We investigated the 
action of suramin on the signal transduction pathways to DNA topoisomerase II 
(Topo II). Suramin showed a growth-inhibitory effect on a human lung cancer cell 
line (PC-9) with an IC50 of about 160 micrograms/ml. Suramin inhibited the 
catalytic activity of Topo II with an IC50 of about 100 micrograms/ml without 
stabilization of the cleavable complex of DNA and Topo II. Suramin decreased the 
phosphorylation of Topo II with an IC50 of 175 micrograms/ml, but did not change 
the degree of Topo II expression. These IC50 values for inhibition of catalytic 
activity and phosphorylation of Topo II were equivalent to the growth-inhibitory 
dose determined by tetrazolium dye assay. Phosphorylation of the tyrosine 
residues of Topo II was not changed by suramin. In the presence of okadaic acid, 
a potent inhibitor of serine/threonine protein phosphatase, suramin also 
decreased the phosphorylation of Topo II, suggesting that the drug did not act 
on the serine/threonine protein phosphatases inhibited by okadaic acid. Suramin 
also inhibited the protein kinase C (PKC) activity of PC-9 cells. These results 
suggest that suramin decreases the phosphorylation of Topo II mediated by PKC. 
This effect of suramin might cause the inhibition of Topo II activity resulting 
in the growth inhibition of tumor cells.