Resveratrol: A novel type of topoisomerase II inhibitor

The Journal of Biological Chemistry
Joyce H LeeJames M Berger

Abstract

Resveratrol, a polyphenol found in various plant sources, has gained attention as a possible agent responsible for the purported health benefits of certain foods, such as red wine. Despite annual multi-million dollar market sales as a nutriceutical, there is little consensus about the physiological roles of resveratrol. One suggested molecular target of resveratrol is eukaryotic topoisomerase II (topo II), an enzyme essential for chromosome segregation and DNA supercoiling homeostasis. Interestingly, resveratrol is chemically similar to ICRF-187, a clinically approved chemotherapeutic that stabilizes an ATP-dependent dimerization interface in topo II to block enzyme activity. Based on this similarity, we hypothesized that resveratrol may antagonize topo II by a similar mechanism. Using a variety of biochemical assays, we find that resveratrol indeed acts through the ICRF-187 binding locus, but that it inhibits topo II by preventing ATPase domain dimerization rather than stabilizing it. This work presents the first comprehensive analysis of the biochemical effects of both ICRF-187 and resveratrol on the human isoforms of topo II, and reveals a new mode for the allosteric regulation of topo II through modulation of ATPase status....Continue Reading

References

Nov 30, 1979·Science·P O Brown, N R Cozzarelli
Jan 1, 1992·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J L SpeyerM Meyers
Oct 25, 1990·Nucleic Acids Research·C Aslanidis, P J de Jong
Apr 26, 1969·Nature·A M CreightonS Whitecross
Apr 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·K MizuuchiM Gellert
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·J RocaJ C Wang
May 1, 1994·Molecular and Cellular Biology·P R CaronJ C Wang
Jan 15, 2000·The Journal of Biological Chemistry·L H JensenJ L Nitiss
Sep 29, 2001·The Journal of Biological Chemistry·K C HuangR M Snapka
Feb 19, 2002·The Journal of Biological Chemistry·Valérie LamourDino Moras
Jul 12, 2002·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·H TapieroG Mathé
Mar 29, 2003·The American Journal of Clinical Nutrition·Charles H Halsted
Jul 31, 2003·Pharmacology & Therapeutics·Annette K LarsenAndrzej Skladanowski
Aug 27, 2003·Nature·Konrad T HowitzDavid A Sinclair
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Scott ClassenJames M Berger
Oct 18, 2003·Journal of Cancer Research and Clinical Oncology·S M Swain, P Vici
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jan 11, 2005·The American Journal of Clinical Nutrition·Louise I MennenAugustin Scalbert
Feb 3, 2005·The Journal of Biological Chemistry·Matt KaeberleinBrian K Kennedy
Mar 8, 2005·The Journal of Biological Chemistry·Margie T BorraJohn M Denu
Mar 31, 2005·Journal of Agricultural and Food Chemistry·Jeong-Youn JoMary Ann Lila
Aug 16, 2005·The Journal of Biological Chemistry·Hua WeiGregory L Verdine
Sep 10, 2005·Journal of Biotechnology·Susanne van den BergHelena Berglund
Mar 16, 2006·Journal of Agricultural and Food Chemistry·Jeong-Youn JoMary Ann Lila
Nov 7, 2006·Nature·Joseph A BaurDavid A Sinclair
Jun 7, 2007·The Biochemical Journal·Sara FröjdöLuciano Pirola
Apr 21, 2009·Nature Reviews. Cancer·John L Nitiss
Mar 23, 2010·Molecular Neurobiology·Albert Y SunGrace Y Sun
Jun 11, 2010·Chemistry & Biology·Yves PommierChristophe Marchand
Jun 21, 2011·Molecular Nutrition & Food Research·James M SmoligaHeather A Hausenblas

❮ Previous
Next ❯

Citations

May 31, 2018·Current Opinion in Clinical Nutrition and Metabolic Care·Anastasia Z KaleaJessica L Buxton
Mar 13, 2020·Neurochemical Research·Yan YanHaibing Yu
Oct 23, 2020·Journal of Biomolecular Structure & Dynamics·Kanika VermaThanyada Rungrotmongkol
Oct 25, 2020·International Journal of Molecular Sciences·Domenico IacopettaMarcello Maggiolini
Oct 7, 2020·Annual Review of Pharmacology and Toxicology·Konrad Teodor SawickiAlessandra Ghigo
Aug 23, 2019·DNA Repair·Karin C NitissLeslyn A Hanakahi
Aug 3, 2019·European Journal of Medicinal Chemistry·Lucia BiasuttoMario Zoratti
Dec 11, 2020·Cancers·Xingjian Zhai, Yassine El Hiani
Feb 23, 2021·Oncotarget·Mikhail V Blagosklonny
Oct 9, 2019·Journal of Medicinal Chemistry·Žiga SkokJanez Ilaš
Oct 5, 2021·Current Protocols·John L NitissNancy Maizels
Oct 29, 2021·Pharmacology Research & Perspectives·Esther P BonittoKerry B Goralski
Sep 7, 2021·Anti-cancer Drugs·Luciana Bicalho Moreira SoaresGlenda Nicioli da Silva

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.