The topoisomerase II-inhibitor NC-190 reduces the level of thymidine kinase mRNA in murine tumor cells

Res Commun Mol Pathol Pharmacol. 2002;111(1-4):77-87.

Abstract

The novel antitumor compound NC-190 strongly inhibited the growth of FM3A cells with an IC50 of 0.019 microg/ml (0.042 microM) when cultured with NC-190 for 48 h. NC-190 potently suppressed DNA synthesis, with 90% inhibition observed at 0.1 microg/ml of NC-190. RNA and protein syntheses were also suppressed under the same conditions, but to a lesser extent. We then measured the cellular enzymatic activities of DNA polymerase alpha, RNA polymerase, thymidine kinase, thymidylate synthase and Leu-tRNA synthetase of FM3A cells cultured with or without NC-190. Of these 5 enzymes, the activity of thymidine kinase was most strongly suppressed by NC-190, by 77%. Although NC-190 did not directly inhibit the activitiy of thymidine kinase in a cell-free system, expression of mRNA of thymidine kinase was suppressed by 75% in NC-190-treated cells. These results indicate that NC-190 can suppress the expression of the gene for thymidine kinase and the inhibition of thymidine kinase contributes to the inhibition of cell growth by NC-190 together with the inhibition of topoisomerase II.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Division
  • Cell Line, Tumor
  • Enzyme Inhibitors / pharmacology*
  • Mammary Neoplasms, Experimental / enzymology
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Phenazines / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Thymidine Kinase / genetics*
  • Topoisomerase II Inhibitors*

Substances

  • Enzyme Inhibitors
  • Phenazines
  • RNA, Messenger
  • Topoisomerase II Inhibitors
  • NC 190
  • Thymidine Kinase