Resveratrol targets G-quadruplexes to exert its pharmacological effects

Ana Soriano-Lerma, Victoria Sanchez-Martin, Javier Murciano-Calles, Matilde Ortiz-Gonzalez, Maria J Tello-Lopez, Virginia Perez-Carrasco, Angel Linde-Rodriguez, Inmaculada Ramirez-Macias, Irene Gomez-Pinto, Inmaculada Lopez-Aliaga, Miguel Soriano, Jose A Garcia-Salcedo
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Abstract

Resveratrol (RSV) is one of the most studied and used biomolecules, for which many pharmacological effects targeting multiple tissues have been described. However, a common underlying mechanism driving its full pharmacological activity has not been elucidated to date. G-quadruplexes (G4s) are non-canonical nucleic acid structures found in promoters and involved in controlling gene transcription. This study demonstrates a G4-dependent mode of action for RSV, explaining its multi-target traits. RSV was shown to stabilise cellular G4s, which accumulate around double strand breaks (DSBs) in the promoters of differentially expressed genes (DEGs). G4 targeting triggers DNA damage and controls gene expression. Unravelling the main mode of action of RSV will be helpful to improve its therapeutic potential in a wide variety of health scenarios.
白藜芦醇以 G-四联体为目标发挥药理作用
白藜芦醇(RSV)是研究和使用最多的生物大分子之一,针对多种组织的许多药理作用已被描述。然而,迄今为止尚未阐明驱动其全部药理活性的共同基本机制。G 型四聚体(G4s)是存在于启动子中的非经典核酸结构,参与控制基因转录。本研究证明了 RSV 依赖于 G4 的作用模式,从而解释了其多靶点特性。研究表明,RSV 能稳定细胞中的 G4,这些 G4 聚集在差异表达基因(DEG)启动子的双链断裂(DSB)周围。G4 靶向触发 DNA 损伤并控制基因表达。揭示 RSV 的主要作用模式将有助于提高其在各种健康状况下的治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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