组蛋白去乙酰化酶抑制剂作为抗乳腺癌药物的新作用。

Emerging role of histone deacetylase inhibitors as anti-breast-cancer agents.

机构信息

Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka.

出版信息

Drug Discov Today. 2019 Mar;24(3):685-702. doi: 10.1016/j.drudis.2019.02.003. Epub 2019 Feb 15.

DOI:10.1016/j.drudis.2019.02.003

PMID:30776482

Abstract

Breast cancer (BC) remains the most frequently diagnosed cancer in women. A balance in the opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs) is necessary for epigenetic regulation of gene expression. Impairment in the balance between the actions of HATs and HDACs has been reported in the development of BC. By targeting histone and several non-histone proteins, histone deacetylase inhibitors (HDACi) can maintain the cellular acetylation profile and reverse the function of several proteins responsible for BC development. Preclinical and clinical data show that HDACi can evoke different anticancer mechanisms in distinct BC types.

摘要

乳腺癌（BC）仍然是女性最常见的癌症。组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（HDACs）的拮抗作用之间的平衡对于基因表达的表观遗传调控是必要的。在 BC 的发展中，已经报道了 HATs 和 HDACs 作用之间的平衡受损。通过针对组蛋白和几种非组蛋白蛋白，组蛋白去乙酰化酶抑制剂（HDACi）可以维持细胞乙酰化谱，并逆转负责 BC 发展的几种蛋白的功能。临床前和临床数据表明，HDACi 可以在不同的 BC 类型中引发不同的抗癌机制。