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  • Title: Induction of topoisomerase I-mediated DNA cleavage by a new indolocarbazole, ED-110.
    Author: Yoshinari T, Yamada A, Uemura D, Nomura K, Arakawa H, Kojiri K, Yoshida E, Suda H, Okura A.
    Journal: Cancer Res; 1993 Feb 01; 53(3):490-4. PubMed ID: 8381047.
    Abstract:
    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.
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