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.