Additive effects of amrubicin with cisplatin on human lung cancer cell lines

Amrubicin (AMR) is a novel, completely synthetic 9-aminoanthracycline derivative. Amrubicinol, the C-13 alcohol metabolite of AMR, inhibits purified human topoisomerase II (topo II). We examined the effect of the combination of cisplatin (CDDP) and amrubicinol in vitro using a small cell lung cancer cell line (SBC-3) and an adenocarcinoma cell line (Ma-1), by WST-1 assay and isobologram analysis. When the two drugs were used together either simultaneously or sequentially, their combined effects were additive. A high concentration of CDDP (300 microM) enhanced the topo II inhibitory activity of amrubicinol as determined by kinetoplast-DNA decatenation assay. On the other hand, amrubicinol increased formation of DNA interstrand cross-links (ICL) in the cells, as determined using ethidium bromide fluorescence binding assay (EBFA), for simultaneous exposure to CDDP (0-300 microM) and amrubicinol (2 microM) compared with CDDP alone. These biological interactions might result in additive interaction between amrubicinol and CDDP.