Laboratory of Molecular and Cellular Biology of Cancer, Kirchberg Hospital, 9, Edward Steichen Street, L-2540 Luxembourg, Luxembourg.
Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, 08826, South Korea.
Pharmacol Res. 2018 Mar;129:337-356. doi: 10.1016/j.phrs.2017.11.004. Epub 2017 Nov 11.
Alterations of the epigenetic machinery, affecting multiple biological functions, represent a major hallmark enabling the development of tumors. Among epigenetic regulatory proteins, histone deacetylase (HDAC)6 has emerged as an interesting potential therapeutic target towards a variety of diseases including cancer. Accordingly, this isoenzyme regulates many vital cellular regulatory processes and pathways essential to physiological homeostasis, as well as tumor multistep transformation involving initiation, promotion, progression and metastasis. In this review, we will consequently discuss the critical implications of HDAC6 in distinct mechanisms relevant to physiological and cancerous conditions, as well as the anticancer properties of synthetic, natural and natural-derived compounds through the modulation of HDAC6-related pathways.
表观遗传机制的改变,影响多种生物功能,是肿瘤发展的主要标志。在表观遗传调控蛋白中,组蛋白去乙酰化酶(HDAC)6 作为一种有前途的治疗靶点,已经在多种疾病中得到了研究,包括癌症。因此,这种同工酶调节着许多重要的细胞调节过程和途径,这些过程和途径对于生理内稳态以及涉及起始、促进、进展和转移的肿瘤多步转化都是必不可少的。在这篇综述中,我们将讨论 HDAC6 在与生理和癌症相关的不同机制中的关键意义,以及通过调节 HDAC6 相关途径,合成、天然和天然衍生化合物的抗癌特性。