Topostatin, a Novel Inhibitor of Topoisomerases I and II Produced by Thermomonospora alba Strain No. 1520: III. Inhibitory Properties

A novel inhibitor of topoisomerases designated as topostatin was isolated from the culture filtrate of Thermomonospora alba strain No. 1520. The inhibitory activity of topostatin was shown to be pH- and temperature-dependent with a maximum around at pH 6 and 28°C. The stability of topostatin decreased with decreasing pH and rising temperature. Topostatin inhibited topoisomerases I and II in a competitive manner with respect to DNA. The inhibitor also inhibited some restriction endonucleases such as ScaI, HindIII and PstI, but not AluI, BamHI, EcoRI, RNase A, DNase I, DNase II and DNA ligase. Topostatin did not induce the nuclear accumulation of p53 protein by DNA damage in the normal human cells.