Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540, Luxembourg, Luxembourg.
Genes Nutr. 2012 Jul;7(3):357-67. doi: 10.1007/s12263-012-0283-9. Epub 2012 Feb 12.
Protein acetylation status results from a balance between histone acetyltransferase and histone deacetylase (HDAC) activities. Alteration of this balance leads to a disruption of cellular integrity and participates in the development of numerous diseases, including cancer. Therefore, modulation of these activities appears to be a promising approach for anticancer therapy. Histone deacetylase inhibitors (HDACi) are epigenetically active drugs that induce the hyperacetylation of lysine residues within histone and non-histone proteins, thus affecting gene expression and cellular processes such as protein-protein interactions, protein stability, DNA binding and protein sub-cellular localization. Therefore, HDACi are promising anti-tumor agents as they may affect the cell cycle, inhibit proliferation, stimulate differentiation and induce apoptotic cell death. Over the last 30 years, numerous synthetic and natural products, including a broad range of dietary compounds, have been identified as HDACi. This review focuses on molecules from natural origins modulating HDAC activities and presenting promising anticancer activities.
蛋白质乙酰化状态是由组蛋白乙酰转移酶和组蛋白去乙酰化酶（HDAC）活性之间的平衡决定的。这种平衡的改变导致细胞完整性的破坏，并参与了许多疾病的发展，包括癌症。因此，调节这些活性似乎是一种有前途的抗癌治疗方法。组蛋白去乙酰化酶抑制剂（HDACi）是具有表观遗传活性的药物，可诱导组蛋白和非组蛋白蛋白中赖氨酸残基的过度乙酰化，从而影响基因表达和细胞过程，如蛋白质-蛋白质相互作用、蛋白质稳定性、DNA 结合和蛋白质亚细胞定位。因此，HDACi 是很有前途的抗肿瘤药物，因为它们可能影响细胞周期、抑制增殖、刺激分化并诱导细胞凋亡。在过去的 30 年中，已经鉴定出许多天然产物，包括广泛的膳食化合物，作为 HDACi。本综述重点介绍了调节 HDAC 活性并具有有前途的抗癌活性的天然来源的分子。
