A carboline derivative as a novel mammalian DNA topoisomerase II targeting agent.
The DNA intercalating, ellipticine analog drug, 5,11-dimethyl-5H-indol[2,3-b]quinoline, is able to stabilize in vitro the topoisomerase II-DNA cleavable complex and to induce DNA breaks in BPV I episome in rat fibroblasts. Cytotoxicity studies with DC3F cells resistant to ellipticine strongly suggest that topoisomerase II is a cellular target involved in the mechanism of cytotoxic action of this carboline derivative.
Pognan
F
F
Laboratoire de Biochimie-Enzymologie, URA 158 du CNRS, U 140 de l'INSERM, Institut Gustave Roussy, Villejuif, France.
Saucier
J M
JM
Paoletti
C
C
Kaczmarek
L
L
Nantka-Namirski
P
P
Mordarski
M
M
Peczynska-Czoch
W
W
D000677:Amsacrine / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002243:Carbolines / Q000494:pharmacology* / Q000633:toxicity; D002417:Cattle; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000187:drug effects* / Q000378:metabolism; D004355:Drug Stability; D007364:Intercalating Agents / Q000494:pharmacology / Q000633:toxicity; D027383:Papillomaviridae / Q000235:genetics; D051381:Rats
D000970:Antineoplastic Agents; D002243:Carbolines; D007364:Intercalating Agents; D000677:Amsacrine; C055575:5,11-dimethyl-5H-indolo(2,3-b)quinoline; D004247:DNA; D004250:DNA Topoisomerases, Type II