Doroshow J H
Proc Natl Acad Sci U S A. 1986 Jun;83(12):4514-8. doi: 10.1073/pnas.83.12.4514.
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.
临床上重要的抗肿瘤醌类药物阿霉素、丝裂霉素C和二氮杂环丁基苯醌对艾氏腹水癌的细胞毒性，可被抗氧化酶过氧化氢酶和超氧化物歧化酶、羟基自由基清除剂二甲亚砜、二乙脲和硫脲以及铁螯合剂去铁胺、2,2-联吡啶和二乙烯三胺五乙酸显著降低或消除。然而，5-亚氨基柔红霉素是一种具有修饰醌功能的阿霉素类似物，可阻止氧化还原循环，测试的任何自由基清除剂均未改善其对肿瘤细胞的杀伤作用。此外，用阿霉素、丝裂霉素C和二氮杂环丁基苯醌而非5-亚氨基柔红霉素处理完整的肿瘤细胞，在体外会产生羟基自由基或相关化学氧化剂，此过程需要过氧化氢、铁和完整的肿瘤细胞。这些结果表明，药物诱导的过氧化氢和羟基自由基生成可能在氧化还原活性抗癌醌类药物的抗肿瘤作用中发挥作用。
