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Biochemistry and Biophysics

Induction of Topoisomerase I-mediated DNA Cleavage by a New Indolocarbazole, ED-110

Tomoko Yoshinari, Akihiro Yamada, Daisuke Uemura, Kazuhiro Nomura, Hiroharu Arakawa, Katsuhisa Kojiri, Eisaku Yoshida, Hiroyuki Suda and Akira Okura
Tomoko Yoshinari
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Akihiro Yamada
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Daisuke Uemura
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Kazuhiro Nomura
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Hiroharu Arakawa
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Katsuhisa Kojiri
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Eisaku Yoshida
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Hiroyuki Suda
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Akira Okura
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DOI:  Published February 1993
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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.

Footnotes

  • ↵1 To whom requests for reprints should be addressed.

  • Received May 18, 1992.
  • Accepted November 10, 1992.
  • ©1993 American Association for Cancer Research.
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February 1993
Volume 53, Issue 3
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Induction of Topoisomerase I-mediated DNA Cleavage by a New Indolocarbazole, ED-110
Tomoko Yoshinari, Akihiro Yamada, Daisuke Uemura, Kazuhiro Nomura, Hiroharu Arakawa, Katsuhisa Kojiri, Eisaku Yoshida, Hiroyuki Suda and Akira Okura
Cancer Res February 1 1993 (53) (3) 490-494;

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Induction of Topoisomerase I-mediated DNA Cleavage by a New Indolocarbazole, ED-110
Tomoko Yoshinari, Akihiro Yamada, Daisuke Uemura, Kazuhiro Nomura, Hiroharu Arakawa, Katsuhisa Kojiri, Eisaku Yoshida, Hiroyuki Suda and Akira Okura
Cancer Res February 1 1993 (53) (3) 490-494;
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