Abstract
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.
Highlights
Resveratrol (3,5,40 -tryhydroxy-stilbene) is a naturally occurring polyphenol found in apples, peanuts, plums, berries, and fruit seeds of Vitis venifera species
It has been described that the anticancer and chemopreventive effects of RSV are associated with activation/upregulation of the mitogen-activated protein kinase (MAPK)
Modification upon chromatin structure such as methylation, acetylation, and phosphorylation have been broadly exploited as key point of understanding epigenetic mechanisms [20]
Summary
Resveratrol (3,5,40 -tryhydroxy-stilbene) is a naturally occurring polyphenol found in apples, peanuts, plums, berries, and fruit seeds of Vitis venifera species. This compound has received worldwide attention due to its role in regulating multiple transduction pathways of several diseases, including cancer, cardiovascular, neurodegerative, and inflammatory diseases [1]. RSV interferes in the different stages of tumors development, such as initiation, promotion, and progression [2]. The role of this compound on angiogenesis and metastasis is described in the literature [3,4]. It has been described that the anticancer and chemopreventive effects of RSV are associated with activation/upregulation of the mitogen-activated protein kinase (MAPK)
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