Histone, deacetylase inhibitor trichostatin a induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells
Histone, deacetylase inhibitor trichostatin a induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells
复制标题
DOI：
10.1002/ijc.10699
复制
发表时间：
2003-02-20
影响因子：
6.4
通讯作者：
Sugimachi, K
中科院分区：
文献类型：
--
作者：
Yamashita, Y;Shimada, M;Sugimachi, K
通过抑制HDAC活性重塑染色质模板是治疗肿瘤的一种潜在的转录治疗方法。一些HDAC抑制剂已经被开发出来，可以在体外调节细胞的生长和分化。我们分析了一种特异而有效的HDAC抑制剂TSA对人肝癌细胞株HepG2和Huh-7的影响。TSA增加了HepG2和Huh-7中乙酰化组蛋白H3和H4的水平。体外抑制细胞增殖，诱导HepG2细胞G(0)/G(1)期停滞，诱导Huh-7细胞凋亡。TSA上调肝脏特异性功能和肝脏富集型转录因子的基因表达。TSA可上调人肝癌细胞株HepG2和Huh-7的氨氮去除速率和白蛋白合成速率。我们的结果表明TSA可以诱导人肝癌细胞系的细胞周期停滞/凋亡和肝细胞分化。(C)2002年Wiley-Liss，Inc.
Remodeling of the chromatin template by inhibition of HDAC activities represents a potential transcriptional therapy for neoplastic disease. A number of HDAC inhibitors that modulate in vitro cell growth and differentiation have been developed. We analyzed the effects of TSA, a specific and potent HDAC inhibitor, on the human hepatoma cell lines HepG2 and Huh-7. TSA increased levels of acetylated histones H3 and H4 in both HepG2 and Huh-7. It inhibited cell proliferation in vitro and induced G(0)/G(1) arrest in HepG2 and apoptosis in Huh-7. Gene expression of liver-specific functions and liver-enriched transcription factors was upregulated by TSA. TSA upregulated the ammonia removal rate and the albumin synthesis rate of HepG2 and Huh-7. Our results indicate that TSA can induce cell-cycle arrest/apoptosis and hepatocyte differentiation in human liver cancer cell lines. (C) 2002 Wiley-Liss, Inc.