文章：

组蛋白去乙酰化酶与癌症：原因和治疗

Histone deacetylases and cancer: causes and therapies

原文发布日期：2001-12-01

DOI: 10.1038/35106079

类型: Review Article

开放获取: 否

要点：

1. Histone acetylation is determined by the activities of two classes of enzyme: histone acetyltransferases (HATs) and histone deacetylases (HDACs).
2. Histones are the core protein components of nucleosomes and their acetylation status regulates, in part, gene expression.
3. Deacetylated histones are generally associated with silencing gene expression; so the acetylation of histones is generally associated with derepression of gene expression.
4. Aberrant acetylation is associated with several solid tumours and haematological malignancies.
5. Several types of compound have been identified that inhibit HDACs and cause accumulation of acetylated histones in normal and tumour tissues. They also inhibit transformed cell growth in vitro and in vivo.
6. Inhibition of HDACs with hydroxamic-acid-based hybrid polar compounds — for example, suberoylanilide hydroxamic acid (SAHA) — alters transcription of very few expressed genes.
7. Several HDAC inhibitors are in clinical trials with cancer patients. They are well tolerated, cause accumulation of acetylated histones in peripheral mononuclear cells and tumours and, more importantly, have clinical activity with objective tumour regression.

要点翻译：

1. 组蛋白乙酰化由两类酶的活性决定：组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（HDACs）。
2. 组蛋白是核小体的核心蛋白质组分，其乙酰化状态在一定程度上调控基因表达。
3. 去乙酰化的组蛋白通常与基因沉默相关，因此组蛋白乙酰化通常与基因表达的去抑制相关。
4. 异常乙酰化与多种实体瘤和血液系统恶性肿瘤相关。  
5. 目前已发现多种化合物可抑制HDACs，导致正常组织和肿瘤组织中乙酰化组蛋白的积累。这些化合物在体外和体内均能抑制转化细胞生长。
6. 使用基于异羟肟酸的杂极性化合物（例如伏立诺他）抑制HDACs仅会改变极少数表达基因的转录。
7. 多种HDAC抑制剂已在癌症患者中开展临床试验。这些药物耐受性良好，可在外周血单核细胞和肿瘤中引起乙酰化组蛋白积累，更重要的是具有临床活性，可实现客观的肿瘤消退。

英文摘要：

Together, histone acetyltransferases and histone deacetylases (HDACs) determine the acetylation status of histones. This acetylation affects the regulation of gene expression, and inhibitors of HDACs have been found to cause growth arrest, differentiation and/or apoptosis of many tumours cells by altering the transcription of a small number of genes. HDAC inhibitors are proving to be an exciting therapeutic approach to cancer, but how do they exert this effect?

摘要翻译： 

组蛋白乙酰转移酶和组蛋白去乙酰化酶（HDACs）共同决定了组蛋白的乙酰化状态。这种乙酰化作用影响基因表达的调控，研究发现HDAC抑制剂能够通过改变少量基因的转录，导致多种肿瘤细胞发生生长停滞、分化和/或凋亡。HDAC抑制剂已被证明是一种令人振奋的癌症治疗手段，但它们是如何发挥这种作用的呢？

原文链接：

Histone deacetylases and cancer: causes and therapies