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

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

M Fukuda  1 , M Inomata, K Nishio, K Fukuoka, F Kanzawa, H Arioka, T Ishida, H Fukumoto, H Kurokawa, M Oka, N Saijo
Affiliations

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

M Fukuda et al. Jpn J Cancer Res. 1996 Oct.

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.

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