Open AccessA New Antitumor Agent Amrubicin Induces Cell Growth Inhibition by Stabilizing Topoisomerase II‐DNA Complex
Author(s) -
Hanada Mitsuharu,
Mizuno Satoko,
Fukushima Akihisa,
Saito Yoshikazu,
Noguchi Toshihiro,
Yamaoka Takashi
Publication year - 1998
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1998.tb00519.x
Subject(s) - topoisomerase , dna , doxorubicin , cell growth , chemistry , metabolite , growth inhibition , microbiology and biotechnology , biochemistry , biology , cancer research , chemotherapy , genetics
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.