Role of hydrogen peroxide and hydroxyl radical formation in the killing of Ehrlich tumor cells by anticancer quinones.

AUTOR(ES)

Doroshow, J H

RESUMO

The cytotoxicity of the clinically important antineoplastic quinones doxorubicin, mitomycin C, and diaziridinylbenzoquinone for the Ehrlich ascites carcinoma was significantly reduced or abolished by the antioxidant enzymes catalase and superoxide dismutase, the hydroxyl radical scavengers dimethyl sulfoxide, diethylurea, and thiourea, and the iron chelators deferoxamine, 2,2-bipyridine, and diethylenetriaminepentaacetic acid. However, tumor cell killing by 5-iminodaunorubicin, a doxorubicin analog with a modified quinone function that prohibits oxidation-reduction cycling, was not ameliorated by any of the free radical scavengers tested. Furthermore, treatment of intact tumor cells with doxorubicin, mitomycin C, and diaziridinylbenzoquinone but not 5-iminodaunorubicin generated the hydroxyl radical, or a related chemical oxidant, in vitro in a process that required hydrogen peroxide, iron, and intact tumor cells. These results suggest that drug-induced hydrogen peroxide and hydroxyl radical production may play a role in the antineoplastic action of redox active anticancer quinones.

Documentos Relacionados

• Human red cells scavenge extracellular hydrogen peroxide and inhibit formation of hypochlorous acid and hydroxyl radical.
• Hydrogen peroxide release and hydroxyl radical formation in mixtures containing mineral fibres and human neutrophils.
• Hydrogen peroxide-mediated toxicity for Leishmania donovani chagasi promastigotes. Role of hydroxyl radical and protection by heat shock.
• Endogenous Superoxide Dismutase Levels Regulate Iron-Dependent Hydroxyl Radical Formation in Escherichia coli Exposed to Hydrogen Peroxide
• Copper, zinc superoxide dismutase catalyzes hydroxyl radical production from hydrogen peroxide.