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.
|
Authors | M Fukuda, M Inomata, K Nishio, K Fukuoka, F Kanzawa, H Arioka, T Ishida, H Fukumoto, H Kurokawa, M Oka, N Saijo |
Journal | Japanese journal of cancer research : Gann
(Jpn J Cancer Res)
Vol. 87
Issue 10
Pg. 1086-91
(Oct 1996)
ISSN: 0910-5050 [Print] Japan |
PMID | 8957068
(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
|