PMID: 9187272Jun 1, 1997Paper

Relationship between lethal effects and topoisomerase II-mediated double-stranded DNA breaks produced by anthracyclines with different sequence specificity

Molecular Pharmacology
M BinaschiF Zunino

Abstract

The role of the site selectivity of topoisomerase II poisoning in the cytotoxic activity of anthracyclines has not been established. In this article, we have thus studied the levels and persistence of double-stranded DNA breaks (DSB) along with the cytotoxic activity in human leukemic HL60 cells of seven anthracyclines, including doxorubicin, daunorubicin, and idarubicin, as well as sugar-modified analogues characterized by an altered sequence specificity. Epimerization at the 3' position of the sugar moiety markedly affected the biological activity; indeed, a dramatic reduction of drug effects was evident for 3'-deamino-3'-epi-hydroxy-4'-deoxy-4'-amino-daunorubicin. The studied analogues could be gathered into three groups based on the DSB/cytotoxicity ratio. At equitoxic concentrations: (a) parent drugs and 3'-deamino-3'-epi-hydroxy-4'-deoxy-4'-amino-daunorubicin endowed with the same sequence specificity stimulated low DSB levels; (b) 3'-epi-daunorubicin and 3'-deamino-4'-deoxy-4'-epi-amino-idarubicin, which have a different sequence specificity, and teniposide (a structurally unrelated poison) stimulated higher amounts of DSB; and (c) 4-demethoxy-3'-deamino-3'-hydroxy-4'-epi-doxorubicin stimulated the highest DSB levels. Fo...Continue Reading

References

May 3, 1977·Biochimica Et Biophysica Acta·F ZuninoV Crescenzi
Jan 1, 1991·Pharmacology & Therapeutics·K W Kohn
Jan 1, 1989·Annual Review of Biochemistry·L F Liu
Nov 1, 1994·The Biochemical Journal·P M Watt, I D Hickson
Jan 1, 1996·Annual Review of Biochemistry·J C Wang

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Citations

Jan 29, 2002·Environmental and Molecular Mutagenesis·Marcelo de Campos NebelMarcela González-Cid
May 14, 2004·Environmental and Molecular Mutagenesis·Mauricio LehmannHeloísa Helena Rodrigues de Andrade
Sep 8, 2006·The Journal of Biological Chemistry·Lyn M HuffTito Fojo
Feb 8, 2007·British Journal of Cancer·A M E BruynzeelF A E Kruyt
Oct 19, 2012·Journal of Biomedical Materials Research. Part a·Ahmed A HarounAmira Gamal-Eldeen
Nov 1, 2006·Expert Opinion on Drug Discovery·Janos Nadas, Duxin Sun
Oct 4, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sabry M AttiaSaleh A Bakheet
Nov 9, 2018·International Journal of Molecular Sciences·Jessica MarinelloGiovanni Capranico
Sep 23, 2003·Anti-cancer Drugs·Ireneusz MajsterekJanusz Blasiak
Aug 6, 2008·Cancer Chemotherapy and Pharmacology·Andrew G JobsonCaroline A Austin
Mar 25, 2006·Cell Death and Differentiation·A RebbaaB L Mirkin
Jun 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xiaohang QiaoJacques Neefjes
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·K H LeeR A DePinho
Nov 26, 2010·Apoptosis : an International Journal on Programmed Cell Death·Ilona SchonnDorothee C Dartsch
Nov 10, 2009·Journal of Cancer Research and Clinical Oncology·Anna LitwiniecDariusz Grzanka
Apr 23, 2010·Biological & Pharmaceutical Bulletin·Raquel Cariño-CortésEduardo Madrigal-Bujaidar
Jan 25, 2020·International Journal of Molecular Sciences·Branislav KuraMonika Bartekova
Apr 14, 2007·Molecular Cancer Therapeutics·Suzanne M CuttsDon R Phillips
Jul 9, 2008·European Journal of Pharmacology·Yevhen FilyakRostyslav Stoika

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