A New Antitumor Agent Amrubicin Induces Cell Growth Inhibition by Stabilizing Topoisomerase II‐DNA Complex

• Mitsuharu Hanada

• Satoko Mizuno

• Akihisa Fukushima

• Yoshikazu Saito

• Toshihiro Noguchi

• Takashi Yamaoka

Abstract

Amrubicin is a novel, completely synthetic 9‐aminoanthracycline derivative. Amrubicin and its C‐13 alcohol metabolite, amrubicinol, inhibited purified human DNA topoisomerase II (topo II). Compared with doxorubicin (DXR), amrubicin and amrubicinol induced extensive DNA‐protein complex formation and double‐strand DNA breaks in CCRF‐CEM cells and KU‐2 cells. In this study, we found that ICRF‐193, a topo II catalytic inhibitor, antagonized both DNA‐protein complex formation and double‐strand DNA breaks induced by amrubicin and amrubicinol. Coordinately, cell growth inhibition induced by amrubicin and amrubicinol, but not that induced by DXR, was antagonized by ICRF‐193. Taken together, these findings indicate that the cell growth‐inhibitory effects of amrubicin and amrubicinol are due to DNA‐protein complex formation followed by double‐strand DNA breaks, which are mediated by topo II.

Journal

• Japanese Journal of Cancer Research

  Japanese Journal of Cancer Research 89 (11), 1229-1238, 1998-11

  Wiley

Keywords

• Cancer Research
• Oncology

Details

• CRID: 1360292619300573440
• NII Article ID: 10008087730
• NII Book ID: AA00690844
• DOI: 10.1111/j.1349-7006.1998.tb00519.x
• ISSN: 09105050
• ISSN: http://id.crossref.org/issn/09105050
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1349-7006.1998.tb00519.x
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1349-7006.1998.tb00519.x
• Web Site: https://search.jamas.or.jp/link/ui/1999110096
• Data Source:
  • Crossref
  • CiNii Articles