A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex |
| |
Authors: | M Hanada S Mizuno A Fukushima Y Saito T Noguchi T Yamaoka |
| |
Affiliation: | Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co., Ltd., Osaka. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|