School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800903, Brazil.
Institute for Pharmaceutical Chemistry and Buchmann Institute for Life Sciences, Goethe-University, D-60438 Frankfurt am Main, Germany.
Nutrients. 2017 Oct 27;9(11):1172. doi: 10.3390/nu9111172.
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 () range was characterized using Isothermal Titration Calorimetry (ITC). The RSV 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.
白藜芦醇（RSV）的化学预防和抗癌作用在文献中被广泛报道。具体来说，涉及表观遗传调控的机制是调节肿瘤发展的有前途的靶点。溴结构域作为表观遗传读取器，通过识别组蛋白尾部赖氨酸乙酰化并促进基因表达来调节组织特异性转录。在这项工作中，我们表明 RSV 是一种泛 BET 抑制剂。使用差示扫描荧光法（DSF），我们表明 RSV 在 100µM 时将 BET 溴结构域的熔点（∆Tm）提高了约 2.0°C。使用等温滴定量热法（ITC）表征了微摩尔离解常数（）范围。RSV 的 值在 BRD4(1) 的情况下为 6.6µM。分子对接提出了 RSV 针对 BRD4(1)的结合模式，模拟了乙酰-赖氨酸相互作用。所有这些结果表明，RSV 还可以通过与 BET 溴结构域相互作用来识别表观遗传读取器结构域。
