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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Bibliographic Details
Published in:Toxicology in vitro Vol. 14; no. 1; pp. 1 - 5
Main Authors: 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
Language:English
Published: Oxford Elsevier Ltd 01.02.2000
Elsevier Science
Subjects:
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
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Summary: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.
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ISSN:0887-2333
1879-3177
DOI:10.1016/S0887-2333(99)00082-X