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

Japanese Journal of Cancer Research : Gann
M FukudaN Saijo

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.

References

Apr 15, 1992·Biochemical Pharmacology·N S Thakkar, C S Potten
Apr 3, 1992·Cell·G I EvanD C Hancock
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P ShawJ Costa
Jul 2, 1992·Nature·D P Lane
Dec 16, 1991·Biochemical and Biophysical Research Communications·C GiannakisP D Zalewski
Jan 1, 1990·International Journal of Immunopharmacology·P WaringA Sjaarda
Feb 1, 1991·Clinical and Experimental Immunology·S J MartinB M Hannigan
Sep 1, 1990·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·W BurschM Tenniswood
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M ScanlonL R Gooding
Jan 1, 1988·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·T Yamada, H Ohyama
Jan 1, 1980·International Review of Cytology·A H WyllieA R Currie
Sep 7, 1994·Journal of the National Cancer Institute·B W Stewart
Jan 1, 1994·Cancer Chemotherapy and Pharmacology·S Okamoto-KuboN Saijo
Jan 17, 1993·Biochimica Et Biophysica Acta·Y OnishiH Kizaki

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Citations

Apr 1, 2010·Expert Opinion on Drug Discovery·Yoichi TakakusagiKengo Sakaguchi
Feb 5, 2008·Chemico-biological Interactions·Smita S MatkarUtha Hellmann-Blumberg
May 19, 2005·Biochemical Pharmacology·Kengo MorohashiFumio Sugawara
Nov 29, 2012·Toxicology and Industrial Health·Serkan YilmazMustafa Celik
Jan 3, 2001·Medicinal Research Reviews·T Ishikawa
Aug 29, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pavel LasákJakub Stýskala

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