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Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases

[Image: see text] Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. To identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for acti...

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Autores principales: Vann, Kendra R., Sedgeman, Carl A., Gopas, Jacob, Golan-Goldhirsh, Avi, Osheroff, Neil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2015
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520624/
https://www.ncbi.nlm.nih.gov/pubmed/26132160
http://dx.doi.org/10.1021/acs.biochem.5b00162
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author Vann, Kendra R.
Sedgeman, Carl A.
Gopas, Jacob
Golan-Goldhirsh, Avi
Osheroff, Neil
author_facet Vann, Kendra R.
Sedgeman, Carl A.
Gopas, Jacob
Golan-Goldhirsh, Avi
Osheroff, Neil
author_sort Vann, Kendra R.
collection PubMed
description [Image: see text] Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. To identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIα. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. On the basis of previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10–100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons. (1) The activity of the metabolites was abrogated by a reducing agent. (2) Compounds inhibited topoisomerase II activity when they were incubated with the enzyme prior to the addition of DNA. (3) Compounds were unable to poison a topoisomerase IIα construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIα. Several of the extracts enhanced enzyme-mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIα. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption.
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spelling pubmed-45206242016-07-01 Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases Vann, Kendra R. Sedgeman, Carl A. Gopas, Jacob Golan-Goldhirsh, Avi Osheroff, Neil Biochemistry [Image: see text] Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. To identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIα. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. On the basis of previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10–100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons. (1) The activity of the metabolites was abrogated by a reducing agent. (2) Compounds inhibited topoisomerase II activity when they were incubated with the enzyme prior to the addition of DNA. (3) Compounds were unable to poison a topoisomerase IIα construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIα. Several of the extracts enhanced enzyme-mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIα. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption. American Chemical Society 2015-07-01 2015-07-28 /pmc/articles/PMC4520624/ /pubmed/26132160 http://dx.doi.org/10.1021/acs.biochem.5b00162 Text en Copyright © 2015 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Vann, Kendra R.
Sedgeman, Carl A.
Gopas, Jacob
Golan-Goldhirsh, Avi
Osheroff, Neil
Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases
title Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases
title_full Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases
title_fullStr Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases
title_full_unstemmed Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases
title_short Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases
title_sort effects of olive metabolites on dna cleavage mediated by human type ii topoisomerases
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520624/
https://www.ncbi.nlm.nih.gov/pubmed/26132160
http://dx.doi.org/10.1021/acs.biochem.5b00162
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