Etoposide catechol is an oxidizable topoisomerase II poison.

Jacob DA, Gibson EG, Mercer SL, Deweese JE
Chem Res Toxicol. 2013 26 (8): 1156-8

PMID: 23863110 · DOI:10.1021/tx400205n

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.

MeSH Terms (8)

Catechols Cytochrome P-450 CYP3A DNA DNA Breaks, Double-Stranded DNA Topoisomerases, Type II Etoposide Humans Oxidation-Reduction

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