Abstract |
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.
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Authors | J H Doroshow |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 83
Issue 12
Pg. 4514-8
(Jun 1986)
ISSN: 0027-8424 [Print] United States |
PMID | 3086887
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Aziridines
- Benzoquinones
- Free Radicals
- Hydroxides
- Mitomycins
- Quinones
- Mitomycin
- Doxorubicin
- Hydrogen Peroxide
- Catalase
- Superoxide Dismutase
- diaziquone
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Topics |
- Animals
- Aziridines
- Benzoquinones
- Carcinoma, Ehrlich Tumor
(drug therapy)
- Catalase
(metabolism)
- Cell Survival
(drug effects)
- Cells, Cultured
- Doxorubicin
- Free Radicals
- Hydrogen Peroxide
- Hydroxides
- Mice
- Mitomycin
- Mitomycins
- Quinones
- Superoxide Dismutase
(metabolism)
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