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.
Yamauchi
Setsuko
S
The First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan. m6640897@msic.med.osaka-cu.ac.jp
Kudoh
Shinzoh
S
Kimura
Tatsuo
T
Hirata
Kazuto
K
Yoshikawa
Junichi
J
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D004247:DNA; C055866:amrubicin; D002945:Cisplatin