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

Abstract
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.
AuthorsM Fukuda, M Inomata, K Nishio, K Fukuoka, F Kanzawa, H Arioka, T Ishida, H Fukumoto, H Kurokawa, M Oka, N Saijo
JournalJapanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 87 Issue 10 Pg. 1086-91 (Oct 1996) ISSN: 0910-5050 [Print] Japan
PMID8957068 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA, Neoplasm
  • DNA, Single-Stranded
  • Nucleosomes
  • Topoisomerase II Inhibitors
  • DNA
Topics
  • DNA (drug effects, genetics)
  • DNA Damage
  • DNA Fragmentation
  • DNA, Neoplasm (drug effects, genetics)
  • DNA, Single-Stranded (drug effects, genetics)
  • HL-60 Cells
  • Humans
  • Nucleosomes
  • Topoisomerase II Inhibitors
  • Tumor Cells, Cultured

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