Induction of apoptosis by a novel copper-based anticancer compound, casiopeina II, in L1210 murine leukaemia and CH1 human ovarian carcinoma cells

The activity of casiopeina II \Cu(1,4-dimethyl-1,10-phenanthroline)(glycine )NO3\ a novel anticancer agent, was tested in two cell lines, L1210 murine leukaemia, CH1 human ovarian carcinoma, cisplatin-resistant and sensitive, Exposure of the cells to a range of concentrations of casiopeina II indicat es that this copper complex kills cells by apoptosis and necrosis, Condense d chromatin and nuclear fragmentation were observed after exposure to casio peina II. The caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD- FMK) almost completely inhibited apoptosis induced by cisplatin; hen-ever, casiopeina II-induced apoptosis was inhibited only by 50-70%. These data ar e consistent with caspase activation (measured by Z-Asp-Glu-Val-Asp-7-amino -4-trifluoromethylcoumarin; Z-DEVD-AFC) by casiopeina II and cisplatin and confirm that caspases are activated in the apoptotic cell death induced by casiopeina II. DNA fragmentation was observed in L1210 cells, but not in CH 1 cells. No difference in susceptibility to induction of apoptosis by casio peina II was found between sensitive and cisplatin resistant cells. In this work we show that the novel copper-based antineoplastic agent casiopeina I I is highly active against murine and human canter cell Lines, including ce ll Lines resistant to cisplatin. (C) 2000 Elsevier Science Ltd. All rights reserved.