Dietary Compound Resveratrol Is a Pan-BET Bromodomain Inhibitor

Nutrients

卷:9

David Heidenreich¹  Stefan Knapp¹  Gabriel Dalio Bernardes da Silva²  Chung Man Chin²  Jean Leandro dos Santos²  Luiz Antonio Dutra² 

[1] Institute for Pharmaceutical Chemistry and Buchmann Institute for Life Sciences, Goethe-University, D-60438 Frankfurt am Main, Germany;

[2] School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800903, Brazil;

关键词: resveratrol;    bromodomains;    epigenetic;    Differential Scanning Calorimetry (DSF);    Isothermal Titration Calorimetry (ITC);   

DOI  :  10.3390/nu9111172

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown