title: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Lipscomb University College of Pharmacy and Health Sciences, Nashville, Tennessee 37204-3951, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Jacob
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Gibson
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mercer
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Deweese
mesh_terms: D002396:Catechols / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism*; D005047:Etoposide / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D010084:Oxidation-Reduction
chemical_list: D002396:Catechols; D005047:Etoposide; D004247:DNA; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D004250:DNA Topoisomerases, Type II; C034221:catechol