Verza Flávia Alves, Das Umashankar, Fachin Ana Lúcia, Dimmock Jonathan R, Marins Mozart
Biotechnology Unit, University of Ribeirão Preto, Ribeirão Preto SP CEP 14096-900, Brazil.
College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, SK S7N 5C9, Canada.
Cancers (Basel). 2020 Jun 23;12(6):1664. doi: 10.3390/cancers12061664.
Histones are the main structural proteins of eukaryotic chromatin. Histone acetylation/ deacetylation are the epigenetic mechanisms of the regulation of gene expression and are catalyzed by histone acetyltransferases (HAT) and histone deacetylases (HDAC). These epigenetic alterations of DNA structure influence the action of transcription factors which can induce or repress gene transcription. The HATs catalyze acetylation and the events related to gene transcription and are also responsible for transporting newly synthesized histones from the cytoplasm to the nucleus. The activity of HDACs is mainly involved in silencing gene expression and according to their specialized functions are divided into classes I, II, III and IV. The disturbance of the expression and mutations of HDAC genes causes the aberrant transcription of key genes regulating important cancer pathways such as cell proliferation, cell-cycle regulation and apoptosis. In view of their role in cancer pathways, HDACs are considered promising therapeutic targets and the development of HDAC inhibitors is a hot topic in the search for new anticancer drugs. The present review will focus on HDACs I, II and IV, the best known inhibitors and potential alternative inhibitors derived from natural and synthetic products which can be used to influence HDAC activity and the development of new cancer therapies.
组蛋白是真核染色质的主要结构蛋白。组蛋白乙酰化/去乙酰化是基因表达调控的表观遗传机制，由组蛋白乙酰转移酶（HAT）和组蛋白去乙酰化酶（HDAC）催化。DNA结构的这些表观遗传改变影响转录因子的作用，转录因子可诱导或抑制基因转录。HAT催化乙酰化以及与基因转录相关的事件，还负责将新合成的组蛋白从细胞质转运到细胞核。HDAC的活性主要参与基因表达的沉默，根据其特定功能可分为I类、II类、III类和IV类。HDAC基因表达的紊乱和突变会导致调节重要癌症途径（如细胞增殖、细胞周期调控和细胞凋亡）的关键基因的异常转录。鉴于它们在癌症途径中的作用，HDAC被认为是有前景的治疗靶点，HDAC抑制剂的开发是寻找新型抗癌药物的热门话题。本综述将聚焦于I类、II类和IV类HDAC，最知名的抑制剂以及源自天然和合成产物的潜在替代抑制剂，这些抑制剂可用于影响HDAC活性以及开发新的癌症治疗方法。
