RT Journal Article SR Electronic T1 Induction of Topoisomerase I-mediated DNA Cleavage by a New Indolocarbazole, ED-110 JF Cancer Research JO Cancer Res FD American Association for Cancer Research SP 490 OP 494 VO 53 IS 3 A1 Yoshinari, Tomoko A1 Yamada, Akihiro A1 Uemura, Daisuke A1 Nomura, Kazuhiro A1 Arakawa, Hiroharu A1 Kojiri, Katsuhisa A1 Yoshida, Eisaku A1 Suda, Hiroyuki A1 Okura, Akira YR 1993 UL http://cancerres.aacrjournals.org/content/53/3/490.abstract AB ED-110 is a new semisynthetic antitumor agent derived from a novel indolocarbazole antibiotic, BE-13793C, produced by an actinomycete. ED-110 induced topoisomerase I-mediated DNA cleavage in vitro as strongly as camptothecin, whereas topoisomerase II-mediated DNA cleavage was not induced by this agent. Exposure of P388 cells to Ed-110 caused a typical topoisomerase toxicity, i.e.: formation of cleavable complexes; inhibition of nucleotide synthesis rather than protein synthesis; and cell cycle arrest in G2. ED-110 inhibited the growth of P388 cells, with a 50% growth-inhibitory concentration of 44 nm. ED-110 is distinguished from camptothecin by its very different structure and its ability to intercalate into double-stranded DNA. These results suggest that ED-110 has potential as a novel antitumor agent targeting topoisomerase I. ©1993 American Association for Cancer Research.