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)NO 3], 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 indic...

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Veröffentlicht in:	Toxicology in vitro Jg. 14; H. 1; S. 1 - 5
Hauptverfasser:	De Vizcaya-Ruiz, A., Rivero-Muller, A., Ruiz-Ramirez, L., Kass, G.E.N., Kelland, L.R., Orr, R.M., Dobrota, M.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Oxford Elsevier Ltd 01.02.2000 Elsevier Science
Schlagworte:	Animals Antineoplastic agents Antineoplastic Agents, Phytogenic - pharmacology apoptosis Apoptosis - drug effects Biological and medical sciences cancer chemotherapy casiopeina II Caspases - metabolism CH1 cells copper complexes DNA Fragmentation - drug effects DNA, Neoplasm - analysis DNA, Neoplasm - isolation & purification Enzyme Activation - drug effects Female General aspects Humans L1210 cells Leukemia L1210 - drug therapy Leukemia L1210 - enzymology Leukemia L1210 - pathology Medical sciences Mice Organometallic Compounds - pharmacology Ovarian Neoplasms - drug therapy Ovarian Neoplasms - enzymology Ovarian Neoplasms - pathology Pharmacology. Drug treatments Tumor Cells, Cultured FBS=foetal bovine serum copper complexes PBS=phosphate buffered saline cancer chemotherapy apoptosis Z-VAD-FMK=Z-Val-Ala-DL-Asp-fluoromethylketone Z-DEVD-AFC=Z-Asp-Glu-Val-Asp-7-amino-4-trifluoromethylcoumarin DMEM=Dulbecco's modified Eagle's medium Antineoplastic agent Human Nitrogen heterocycle Rodentia Nitrato complex Organic ligand Cytotoxicity L1210-Leukemia Transition metal Complexes Glycine Copper Complexes In vitro Ovary α-Aminoacid Vertebrata Mammalia Cell line Mouse Cell death Complexes Mixed Animal Mechanism of action Tumor cell Apoptosis
ISSN:	0887-2333, 1879-3177
Online-Zugang:	Volltext
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Zusammenfassung:	The activity of casiopeina II [Cu(1,4-dimethyl-1,10-phenanthroline)(glycine)NO 3], 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 indicates that this copper complex kills cells by apoptosis and necrosis. Condensed chromatin and nuclear fragmentation were observed after exposure to casiopeina II. The caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD-FMK) almost completely inhibited apoptosis induced by cisplatin; however, casiopeina II-induced apoptosis was inhibited only by 50–70%. These data are 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 CH1 cells. No difference in susceptibility to induction of apoptosis by casiopeina II was found between sensitive and cisplatin resistant cells. In this work we show that the novel copper-based antineoplastic agent casiopeina II is highly active against murine and human cancer cell lines, including cell lines resistant to cisplatin.
Bibliographie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0887-2333 1879-3177
DOI:	10.1016/S0887-2333(99)00082-X