Dietary compound resveratrol is a pan-BET bromodomain inhibitor
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/nu9111172 http://hdl.handle.net/11449/179311 |
Resumo: | The chemopreventive and anticancer effects of resveratrol (RSV) are widely reported in the literature. Specifically, mechanisms involving epigenetic regulation are promising targets to regulate tumor development. Bromodomains act as epigenetic readers by recognizing lysine acetylation on histone tails and boosting gene expression in order to regulate tissue-specific transcription. In this work, we showed that RSV is a pan-BET inhibitor. Using Differential Scanning Fluorimetry (DSF), we showed that RSV at 100μM increased the melting temperature (ΔTm) of BET bromodomains by around 2.0ᵒC. The micromolar dissociation constant (Kd) range was characterized using Isothermal Titration Calorimetry (ITC). The RSV Kd value accounted to 6.6 μM in case of BRD4(1). Molecular docking proposed the binding mode of RSV against BRD4(1) mimicking the acetyl-lysine interactions. All these results suggest that RSV can also recognize epigenetic readers domains by interacting with BET bromodomains. |
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Dietary compound resveratrol is a pan-BET bromodomain inhibitorBromodomainsDifferential Scanning Calorimetry (DSF)EpigeneticIsothermal Titration Calorimetry (ITC)ResveratrolThe chemopreventive and anticancer effects of resveratrol (RSV) are widely reported in the literature. Specifically, mechanisms involving epigenetic regulation are promising targets to regulate tumor development. Bromodomains act as epigenetic readers by recognizing lysine acetylation on histone tails and boosting gene expression in order to regulate tissue-specific transcription. In this work, we showed that RSV is a pan-BET inhibitor. Using Differential Scanning Fluorimetry (DSF), we showed that RSV at 100μM increased the melting temperature (ΔTm) of BET bromodomains by around 2.0ᵒC. The micromolar dissociation constant (Kd) range was characterized using Isothermal Titration Calorimetry (ITC). The RSV Kd value accounted to 6.6 μM in case of BRD4(1). Molecular docking proposed the binding mode of RSV against BRD4(1) mimicking the acetyl-lysine interactions. All these results suggest that RSV can also recognize epigenetic readers domains by interacting with BET bromodomains.School of Pharmaceutical Sciences São Paulo State University (UNESP)Institute for Pharmaceutical Chemistry and Buchmann Institute for Life Sciences Goethe-UniversitySchool of Pharmaceutical Sciences São Paulo State University (UNESP)Universidade Estadual Paulista (Unesp)Goethe-UniversityDutra, Luiz Antonio [UNESP]Heidenreich, Davidda Silva, Gabriel Dalio Bernardes [UNESP]Chin, Chung Man [UNESP]Knapp, Stefandos Santos, Jean Leandro [UNESP]2018-12-11T17:34:40Z2018-12-11T17:34:40Z2017-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.3390/nu9111172Nutrients, v. 9, n. 11, 2017.2072-6643http://hdl.handle.net/11449/17931110.3390/nu91111722-s2.0-850325664832-s2.0-85032566483.pdf97343336079754130000-0003-4141-0455Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNutrients1,557info:eu-repo/semantics/openAccess2023-12-13T06:20:17Zoai:repositorio.unesp.br:11449/179311Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-13T06:20:17Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Dietary compound resveratrol is a pan-BET bromodomain inhibitor |
title |
Dietary compound resveratrol is a pan-BET bromodomain inhibitor |
spellingShingle |
Dietary compound resveratrol is a pan-BET bromodomain inhibitor Dutra, Luiz Antonio [UNESP] Bromodomains Differential Scanning Calorimetry (DSF) Epigenetic Isothermal Titration Calorimetry (ITC) Resveratrol |
title_short |
Dietary compound resveratrol is a pan-BET bromodomain inhibitor |
title_full |
Dietary compound resveratrol is a pan-BET bromodomain inhibitor |
title_fullStr |
Dietary compound resveratrol is a pan-BET bromodomain inhibitor |
title_full_unstemmed |
Dietary compound resveratrol is a pan-BET bromodomain inhibitor |
title_sort |
Dietary compound resveratrol is a pan-BET bromodomain inhibitor |
author |
Dutra, Luiz Antonio [UNESP] |
author_facet |
Dutra, Luiz Antonio [UNESP] Heidenreich, David da Silva, Gabriel Dalio Bernardes [UNESP] Chin, Chung Man [UNESP] Knapp, Stefan dos Santos, Jean Leandro [UNESP] |
author_role |
author |
author2 |
Heidenreich, David da Silva, Gabriel Dalio Bernardes [UNESP] Chin, Chung Man [UNESP] Knapp, Stefan dos Santos, Jean Leandro [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Goethe-University |
dc.contributor.author.fl_str_mv |
Dutra, Luiz Antonio [UNESP] Heidenreich, David da Silva, Gabriel Dalio Bernardes [UNESP] Chin, Chung Man [UNESP] Knapp, Stefan dos Santos, Jean Leandro [UNESP] |
dc.subject.por.fl_str_mv |
Bromodomains Differential Scanning Calorimetry (DSF) Epigenetic Isothermal Titration Calorimetry (ITC) Resveratrol |
topic |
Bromodomains Differential Scanning Calorimetry (DSF) Epigenetic Isothermal Titration Calorimetry (ITC) Resveratrol |
description |
The chemopreventive and anticancer effects of resveratrol (RSV) are widely reported in the literature. Specifically, mechanisms involving epigenetic regulation are promising targets to regulate tumor development. Bromodomains act as epigenetic readers by recognizing lysine acetylation on histone tails and boosting gene expression in order to regulate tissue-specific transcription. In this work, we showed that RSV is a pan-BET inhibitor. Using Differential Scanning Fluorimetry (DSF), we showed that RSV at 100μM increased the melting temperature (ΔTm) of BET bromodomains by around 2.0ᵒC. The micromolar dissociation constant (Kd) range was characterized using Isothermal Titration Calorimetry (ITC). The RSV Kd value accounted to 6.6 μM in case of BRD4(1). Molecular docking proposed the binding mode of RSV against BRD4(1) mimicking the acetyl-lysine interactions. All these results suggest that RSV can also recognize epigenetic readers domains by interacting with BET bromodomains. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-11-01 2018-12-11T17:34:40Z 2018-12-11T17:34:40Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/nu9111172 Nutrients, v. 9, n. 11, 2017. 2072-6643 http://hdl.handle.net/11449/179311 10.3390/nu9111172 2-s2.0-85032566483 2-s2.0-85032566483.pdf 9734333607975413 0000-0003-4141-0455 |
url |
http://dx.doi.org/10.3390/nu9111172 http://hdl.handle.net/11449/179311 |
identifier_str_mv |
Nutrients, v. 9, n. 11, 2017. 2072-6643 10.3390/nu9111172 2-s2.0-85032566483 2-s2.0-85032566483.pdf 9734333607975413 0000-0003-4141-0455 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nutrients 1,557 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1799965271758209024 |