Dietary Compound Resveratrol Is a Pan-BET Bromodomain Inhibitor

• Main Authors: Luiz Antonio Dutra, David Heidenreich, Gabriel Dalio Bernardes da Silva, Chung Man Chin, Stefan Knapp, Jean Leandro dos Santos
• Format: Article
• Language: English
• Published: MDPI AG 2017-10-01
• Series: Nutrients
• Subjects: resveratrol; bromodomains; epigenetic; Differential Scanning Calorimetry (DSF); Isothermal Titration Calorimetry (ITC)
• Online Access: https://www.mdpi.com/2072-6643/9/11/1172

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.