A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex.

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Hanada M, Mizuno S, Fukushima A, Saito Y, Noguchi T, Yamaoka T

A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex.

Jpn J Cancer Res. 1998 Nov;89(11):1229-38.

PubMed ID
9914793 [ View in PubMed
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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.

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