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
相关论文
共 50 条
  • [21] Treatment of lymphoid cells with the topoisomerase II poison etoposide leads to an increased juxtaposition of AML1 and ETO genes on the surface of nucleoli
    Rubtsov, M. A.
    Allinne, J.
    Vassetzky, Y. S.
    Razin, S. V.
    Iarovaia, O. V.
    FEBS JOURNAL, 2011, 278 : 336 - 336
  • [22] Mitoxantrone, More than Just Another Topoisomerase II Poison
    Evison, Benny J.
    Sleebs, Brad E.
    Watson, Keith G.
    Phillips, Don R.
    Cutts, Suzanne M.
    MEDICINAL RESEARCH REVIEWS, 2016, 36 (02) : 248 - 299
  • [23] Phenanthriplatin Acts As a Covalent Poison of Topoisomerase II Cleavage Complexes
    Riddell, Imogen A.
    Agama, Keli
    Park, Ga Young
    Pommier, Yves
    Lippard, Stephen J.
    ACS CHEMICAL BIOLOGY, 2016, 11 (11) : 2996 - 3001
  • [24] Resveratrol acts as a topoisomerase II poison in human glioma cells
    Leone, Stefano
    Basso, Emiliano
    Polticelli, Fabio
    Cozzi, Renata
    INTERNATIONAL JOURNAL OF CANCER, 2012, 131 (03) : E173 - E178
  • [25] Alternariol acts as a topoisomerase poison, preferentially affecting the IIα isoform
    Fehr, Markus
    Pahlke, Gudrun
    Fritz, Jessica
    Christensen, Morten O.
    Boege, Fritz
    Altemoeller, Martina
    Podlech, Joachim
    Marko, Doris
    MOLECULAR NUTRITION & FOOD RESEARCH, 2009, 53 (04) : 441 - 451
  • [26] The Broken MLL Gene Is Frequently Located Outside the Inherent Chromosome Territory in Human Lymphoid Cells Treated with DNA Topoisomerase II Poison Etoposide
    Glukhov, Sergey I.
    Rubtsov, Mikhail A.
    Alexeyevsky, Daniil A.
    Alexeevski, Andrei V.
    Razin, Sergey V.
    Iarovaia, Olga V.
    PLOS ONE, 2013, 8 (09):
  • [27] Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase II α gene transfer is independent of topoisomerase II β
    Z Zhou
    L A Zwelling
    R Ganapathi
    E S Kleinerman
    British Journal of Cancer, 2001, 85 : 747 - 751
  • [28] Down-regulation of topoisomerase II by camptothecin does not prevent additive activity of the topoisomerase II inhibitor etoposide in vitro
    Stahl, M
    KasimirBauer, S
    Harstrick, A
    ANTI-CANCER DRUGS, 1997, 8 (07) : 671 - 676
  • [29] Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase IIα gene transfer is independent of topoisomerase IIβ
    Zhou, Z
    Zwelling, LA
    Ganapathi, R
    Kleinerman, ES
    BRITISH JOURNAL OF CANCER, 2001, 85 (05) : 747 - 751
  • [30] Structural and Biochemical Basis of Etoposide-Resistant Mutations in Topoisomerase IIα
    Gibson, Elizabeth G.
    Deweese, Joseph E.
    SYMMETRY-BASEL, 2022, 14 (07):
12345