Effects of Ukrain on the activities of DNA-nicking enzymes.
We studied the effects of Ukrain, a novel antitumor drug, on the activities of calcium, magnesium-dependent endonuclease (CME) and manganese-dependent endonuclease (MnDE) in rat liver nuclei, the activity of topoisomerase I assessed by pUC19 plasmid relaxation and CME activity in the nuclei of lymphocytes from colon cancer patients. Ukrain was found to exert a dose-dependent inhibiting effect on both CME and MnDE, similar to that exerted by erythropoietin, which was used as a reference preparation. Both Ukrain and erythropoietin also caused dose-dependent inhibition of topoisomerase I activity. The influence of Ukrain on CME activity in the nuclei of the lymphocytes of colon cancer patients was differential, depending on treatment efficacy. The results suggest that DNA-nicking enzymes may be a target of Ukrain and may mediate its antitumor effects.
Votrin
I I
II
Institute of Biological and Medical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia.
Voltchek
I V
IV
Kurochkin
S N
SN
Kolobkov
S L
SL
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001600:Berberine Alkaloids; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010617:Phenanthridines; D051381:Rats; D011994:Recombinant Proteins
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D001600:Berberine Alkaloids; D010617:Phenanthridines; D011994:Recombinant Proteins; D004921:Erythropoietin; C060921:ukrain; D004706:Endodeoxyribonucleases; C029367:calcium magnesium dependent endodeoxyribonuclease; D004264:DNA Topoisomerases, Type I