Glauben Rainer, Sonnenberg Elena, Zeitz Martin, Siegmund Britta
Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Medical Department I, Berlin, Germany.
Cancer Lett. 2009 Aug 8;280(2):154-9. doi: 10.1016/j.canlet.2008.11.019. Epub 2008 Dec 19.
Histone deacetylase (HDAC) inhibitors have been described in detail for their anti-proliferative potency. Recently, an anti-inflammatory property was characterized in vitro and in vivo. This dual efficacy of HDAC inhibitors is highly attractive, since chronic inflammations such as ulcerative colitis are associated with an increased risk of developing carcinomas. Additionally, in models of colitis and inflammation-induced tumorigenesis inflammation as well as tumor development was significantly inhibited by HDAC inhibitor treatment. The mechanisms involved reach beyond the simple regulation of histone acetylation and deacetylation. The currently known key target structures and mechanisms mediating this dual effect will be discussed in this review.
组蛋白去乙酰化酶(HDAC)抑制剂因其抗增殖能力已得到详细描述。最近,其抗炎特性在体内外得到了表征。HDAC抑制剂的这种双重功效极具吸引力,因为诸如溃疡性结肠炎等慢性炎症与患癌风险增加相关。此外,在结肠炎和炎症诱导的肿瘤发生模型中,HDAC抑制剂治疗可显著抑制炎症以及肿瘤发展。所涉及的机制超出了组蛋白乙酰化和去乙酰化的简单调节。本综述将讨论目前已知的介导这种双重作用的关键靶标结构和机制。