DNA topoisomerase II from mammalian mitochondria is inhibited by the antitumor drugs, m-AMSA and VM-26.
A type II DNA topoisomerase has been partially purified from calf thymus mitochondria by a combination of differential centrifugation and column chromatography. The mitochondrial enzyme was inhibited by amsacrine (m-AMSA) slightly at 0.5 microM, significantly at 5.0 microM, and completely at 50 microM. A similar profile was obtained with teniposide (VM-26) although the latter drug was not quite as potent an inhibitor as the former. P4 unknotting assays of the purified nuclear type II topoisomerase in the presence of m-AMSA and VM-26 indicated that the mitochondrial and nuclear enzymes behaved similarly, although the mitochondrial enzyme appeared to be inhibited more strongly.
Lin
J H
JH
Department of Biochemistry, Eastern Virginia Medical School, Norfolk 23507-1696.
Castora
F J
FJ
D000677:Amsacrine / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002498:Centrifugation; D002845:Chromatography; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D013713:Teniposide / Q000494:pharmacology*; D013950:Thymus Gland / Q000201:enzymology; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D013713:Teniposide; D004259:DNA-Directed DNA Polymerase