文章基本信息

标题：Dietary Compound Resveratrol Is a Pan-BET Bromodomain Inhibitor
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作者：Luiz Antonio Dutra ; David Heidenreich ; Gabriel Dalio Bernardes da Silva 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2017
卷号：9
期号：11
页码：1172
DOI：10.3390/nu9111172
语种：English
出版社：MDPI Publishing
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.
关键词：resveratrol; bromodomains; epigenetic; Differential Scanning Calorimetry (DSF); Isothermal Titration Calorimetry (ITC) resveratrol ; bromodomains ; epigenetic ; Differential Scanning Calorimetry (DSF) ; Isothermal Titration Calorimetry (ITC)