alexa NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals.


Biochemistry & Physiology: Open Access

Author(s): Bachur NR, Gordon SL, Gee MV, Kon H

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Abstract With NADPH as the electron donor, rat liver NADPH cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC catalyzes the single-electron reduction of several quinone antibiotics to a semiquinone or free radical state. The benzanthraquinones adriamycin, daunorubicin, carminomycin, 7-O-methylnogalarol, and aclacinomycin A and the N-heterocyclic quinones streptonigrin and mitomycin C are activated to free radical intermediates which can transfer their single electron to molecular oxygen to form superoxide. The overall Km range for this electron transfer is 0.4 to 42.1 X 10(-4) M. We postulate that the formation of the "site-specific free radical/ intermediate is central to the cytotoxic action of these antibiotics.
This article was published in Proc Natl Acad Sci U S A and referenced in Biochemistry & Physiology: Open Access

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