Cytotoxicity of a low molecular weight Cu2Zn2 superoxide dismutase active center analog in human erythroleukemia cells.
The cytotoxicity of SOD-mimics was studied in human K562 erythroleukemia cells. CuPUPY, a low molecular weight copper complex with properties typical of a Cu2Zn2 SOD active center analog was shown to display pronounced toxicity upon incubation with human K562 erythroleukemia cells, while the ligand, CuSO4 or CuEDTA did not affect vitality. Externally added catalase decreased the cytotoxic effects of CuPUPY by 50% indicating an involvement of hydrogen peroxide in toxicity. An increased oxygen uptake and glutathione oxidation by K562 cells in the presence of CuPUPY suggested that toxicity might be due to a copper-mediated redox-cycle. In fact addition of glutathione to a solution of CuPUPY resulted in glutathione oxidation, O2-consumption and H2O2-generation. CuPUPY proved to be less toxic to human lymphocytes than to K562 cells. This selectivity may be related to the low content of antioxidative enzymes in K562 cells.
Steinkühler
C
C
Physiologisch-chemisches Institut, University of Tübingen, Federal Republic of Germany.
Mavelli
I
I
Rossi
L
L
Pedersen
J Z
JZ
Melino
G
G
Weser
U
U
Rotilio
G
G
D001665:Binding Sites; D002374:Catalase / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007093:Imidazoles / Q000633:toxicity; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology / Q000633:toxicity*; D010101:Oxygen Consumption / Q000187:drug effects; D012545:Schiff Bases / Q000494:pharmacology / Q000633:toxicity*; D013482:Superoxide Dismutase; D014407:Tumor Cells, Cultured
D007093:Imidazoles; D009942:Organometallic Compounds; D012545:Schiff Bases; C064003:1,8-di-(2-imidazoyl)-2,7-diazoctadiene-1,7-(N,N',N'',N''')-Cu(II)diperchlorate; C064004:N,N'-bis(2-pyridylmethylene)-1,4-butanediamine (N,N',N'',N''')-Cu(II)diperchlorate; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione