Etoposide catechol is an oxidizable topoisomerase II poison.

Abstract:

: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 ∼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.

journal_name

Chem Res Toxicol

authors

Jacob DA,Gibson EG,Mercer SL,Deweese JE

doi

10.1021/tx400205n

subject

Has Abstract

pub_date

2013-08-19 00:00:00

pages

1156-8

issue

8

eissn

0893-228X

issn

1520-5010

journal_volume

26

pub_type

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