A topoisomerase II inhibitor, NK109, induces DNA single- and double-strand breaks and apoptosis

Jpn J Cancer Res. 1996 Oct;87(10):1086-91. doi: 10.1111/j.1349-7006.1996.tb03114.x.


2,3-(Methylenedioxy)-5-methyl-7-hydroxy-8-methoxybenzo[c]phenanthr idinium hydrogensulfate dihydrate, called NK109, is a benzo[c]phenanthridine derivative, which inhibits DNA topoisomerase II activity by stabilizing the DNA-enzyme-drug complex, and shows strong growth-inhibitory effects on several human cancer cells. In the present study, NK109 treatment induced DNA fragmentation and a rise in the level of cytoplasmic nucleosomes, which are markers of apoptosis, in human small-cell lung carcinoma SBC-3 cells. These effects were inhibited by zinc ions and enhanced by cycloheximide or actinomycin D. Dose-dependent single- and double-strand DNA breaks were observed, using alkaline and neutral elution assays, in SBC-3 cells treated with more than 0.2 microM NK109 for 4 h. Treatment with NK109 caused more DNA single- and double-strand breaks than treatment with an equimolar amount of VP-16. These results suggest that NK109 induces DNA strand breaks and apoptosis. In addition, it appears that this process does not require protein or RNA synthesis, but involves a specific endonuclease which is inhibited by zinc ions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / drug effects*
  • DNA / genetics
  • DNA Damage*
  • DNA Fragmentation*
  • DNA, Neoplasm / drug effects*
  • DNA, Neoplasm / genetics
  • DNA, Single-Stranded / drug effects
  • DNA, Single-Stranded / genetics
  • HL-60 Cells
  • Humans
  • Nucleosomes
  • Topoisomerase II Inhibitors*
  • Tumor Cells, Cultured


  • DNA, Neoplasm
  • DNA, Single-Stranded
  • Nucleosomes
  • Topoisomerase II Inhibitors
  • DNA