Prevention of doxorubicin-induced killing of MCF-7 human breast cancer cells by oxygen radical scavengers and iron chelating agents.

This study investigated the effect of oxygen radical scavengers and iron chelating agents on the toxicity of doxorubicin for MCF-7 human breast cancer cells. Superoxide dismutase and catalase, but not the heat-inactivated enzymes, the hydroxyl radical scavenger N-acetylcysteine, and the organoselenium compound 2-phenyl-1-2-benzisoselenazol-3(2H)-one, which possesses glutathione peroxidase-like activity, significantly reduced or abolished tumor cell killing by doxorubicin. Similar protective activity was found only for those iron chelating agents capable of penetrating the tumor cell plasma membrane. These experiments suggest that an iron-dependent oxygen radical cascade contributes to the antineoplastic action of the anthracycline antibiotic doxorubicin.