This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoshinari, T. Articles by Okura, A. Search for Related Content PubMed PubMed Citation Articles by Yoshinari, T. Articles by Okura, A.

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

Banyu Tsukuba Research Institute in Collaboration with Merck Research Laboratories, Okubo 3, Tsukuba 300-33 [T. Y., H. A., K. K., H. S., A. O.]; Faculty of Liberal Arts. Shizuoka University, 836 Ohya, Shizuoka 422 [A. Y., D. U.]; and National Cancer Center, 1-5-5 Tsukiji, Chuoh-ku, Tokyo 104 [K. N.], Japan

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.

¹ To whom requests for reprints should be addressed.

Received 5/18/92. Accepted 11/10/92.

This article has been cited by other articles:

				A. Y. Chen, S.-J. Shih, M. Hsiao, M. L. Rothenberg, and M. Prudhomme Induction of Radiosensitization by Indolocarbazole Derivatives: The Role of DNA Topoisomerase I Mol. Pharmacol., September 1, 2004; 66(3): 553 - 560. [Abstract] [Full Text] [PDF]

				Y. Urasaki, G. Laco, Y. Takebayashi, C. Bailly, G. Kohlhagen, and Y. Pommier Use of Camptothecin-resistant Mammalian Cell Lines to Evaluate the Role of Topoisomerase I in the Antiproliferative Activity of the Indolocarbazole, NB-506, and Its Topoisomerase I Binding Site Cancer Res., January 1, 2001; 61(2): 504 - 508. [Abstract] [Full Text]

				H. Komatani, M. Morita, N. Sakaizumi, K. Fukasawa, E. Yoshida, A. Okura, T. Yoshinari, and S. Nishimura A New Mechanism of Acquisition of Drug Resistance by Partial Duplication of Topoisomerase I Cancer Res., June 1, 1999; 59(11): 2701 - 2708. [Abstract] [Full Text] [PDF]

				C. Bailly, L. Dassonneville, P. Colson, C. Houssier, K. Fukasawa, S. Nishimura, and T. Yoshinari Intercalation into DNA Is Not Required for Inhibition of Topoisomerase I by Indolocarbazole Antitumor Agents Cancer Res., June 1, 1999; 59(12): 2853 - 2860. [Abstract] [Full Text] [PDF]

				C. Bailly, P. Colson, C. Houssier, E. Rodrigues-Pereira, M. Prudhomme, and M. J. Waring Recognition of Specific Sequences in DNA by a Topoisomerase I Inhibitor Derived from the Antitumor Drug Rebeccamycin Mol. Pharmacol., January 1, 1998; 53(1): 77 - 87. [Abstract] [Full Text]