Sanaei Masumeh, Kavoosi Fraidoon
Research Center for Non-communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran.
Iran J Pharm Res. 2021 Summer;20(3):324-336. doi: 10.22037/ijpr.2021.115105.15197.
Epigenetics is the study of heritable modifications in gene expression and reversible forms of gene regulation. Recent works have indicated that epigenetics plays a significant role in many types of human cancers hepatocellular carcinoma (HCC). Diverse cellular functions are regulated by histone acetylation and deacetylation. Histone deacetylases (HDACs) and histone acetylases (HATs) are enzymes involved in chromatin remodeling histone deacetylation and acetylation respectively. Aberrant protein acetylation, particularly histone deacetylation, has been reported in a broad range of human cancer types. Epigenetic modification by inhibiting HDAC activity is an emerging approach in cancer treatment. HDACIs play their apoptotic roles through multiple mechanisms such as extrinsic/cytoplasmic and intrinsic/mitochondrial molecular mechanisms. Here, we summarize the major classes of HDACs and epigenetic compounds, HDACIs, and also their molecular mechanisms in HCC including intrinsic and extrinsic apoptotic pathways. An online search of different sources including PubMed, ISI, and Scopus was achieved to find suitable data on mechanisms and pathways of HDACs and HDACIs in HCC. The result demonstrated that the dysregulation of HDACs because of histone deacetylation induces HCC. The histone deacetylation can be reversed by HDACIs resulting in apoptosis induction. In conclusion, because histone deacetylation is a potentially reversible change, epigenetic histone modification represents new opportunities for cancer management by reactivation of gene silencing. The inhibition of HDACs by GDACIs can effectively induce apoptosis and suppress cancer cell proliferation. These compounds can engage both intrinsic and extrinsic apoptotic pathways.
表观遗传学是对基因表达中的可遗传修饰和基因调控的可逆形式的研究。最近的研究表明，表观遗传学在多种人类癌症（包括肝细胞癌，HCC）中发挥着重要作用。多种细胞功能受组蛋白乙酰化和去乙酰化的调节。组蛋白去乙酰化酶（HDACs）和组蛋白乙酰化酶（HATs）分别是参与染色质重塑、组蛋白去乙酰化和乙酰化的酶。在广泛的人类癌症类型中都报道了异常的蛋白质乙酰化，特别是组蛋白去乙酰化。通过抑制HDAC活性进行表观遗传修饰是癌症治疗中的一种新兴方法。HDAC抑制剂（HDACIs）通过多种机制发挥其凋亡作用，如外在/细胞质和内在/线粒体分子机制。在这里，我们总结了HDACs和表观遗传化合物（HDACIs）的主要类别，以及它们在HCC中的分子机制，包括内在和外在凋亡途径。通过在线搜索不同来源，包括PubMed、ISI和Scopus，以找到关于HDACs和HDACIs在HCC中的机制和途径的合适数据。结果表明，由于组蛋白去乙酰化导致的HDACs失调会诱发HCC。HDACIs可以逆转组蛋白去乙酰化，从而诱导细胞凋亡。总之，由于组蛋白去乙酰化是一种潜在的可逆变化，表观遗传组蛋白修饰为通过重新激活基因沉默来管理癌症提供了新的机会。GDACIs对HDACs的抑制可以有效诱导细胞凋亡并抑制癌细胞增殖。这些化合物可以参与内在和外在凋亡途径。
