TY  - JOUR
A1  - Dutra, Luiz Antonio
A1  - Heidenreich, David Jonas
A1  - Bernardes da Silva, Gabriel Dalio
A1  - Chin, Chung Man
A1  - Knapp, Stefan
A1  - Santos, Jean Leandro dos
T1  - Dietary compound resveratrol is a pan-BET bromodomain inhibitor
T2  - Nutrients
N2  - 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 100 µM increased the melting temperature (∆Tm) of BET bromodomains by around 2.0 °C. 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.
KW  - resveratrol
KW  - bromodomains
KW  - epigenetic
KW  - Differential Scanning Calorimetry (DSF)
KW  - Isothermal Titration Calorimetry (ITC)
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44500
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-445009
SN  - 2072-6643
N1  - © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
VL  - 9
IS  - 1172
ER  -