Etoposide Catechol Is an Oxidizable Topoisomerase II Poison

被引：18
|
作者：
Jacob, David A. [1 ]
Gibson, Elizabeth G. [1 ]
Mercer, Susan L. [1 ,2 ]
Deweese, Joseph E. [1 ,3 ]
机构：
[1] Lipscomb Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Nashville, TN 37204 USA
[2] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA
来源：
CHEMICAL RESEARCH IN TOXICOLOGY | 2013年 / 26卷 / 08期
关键词：
O-DEMETHYLATION; DNA CLEAVAGE; QUINONE; METABOLITES; LEUKEMIA; ALPHA;
D O I：
10.1021/tx400205n
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Topoisomerase II regulates DNA topology by generating transient double-stranded breaks. The anticancer drug etoposide targets topoisomerase II and is associated with the formation of secondary leukemias in patients. The quinone and catechol metabolites of etoposide may contribute to strand breaks that trigger leukemic translocations. To further analyze the characteristics of etoposide metabolites, we extend our previous analysis of etoposide quinone to the catechol. We demonstrate that the catechol is similar to 2-3-fold more potent than etoposide and under oxidative reaction conditions induces high levels of double-stranded DNA cleavage. These results support a role for etoposide catechol in contributing to therapy-induced DNA damage.
引用
收藏
页码：1156 / 1158
页数：3
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