Department of Life Sciences, Tzu-Chi University, Hualien, Taiwan.
Biochem Biophys Res Commun. 2012 Jan 20;417(3):1093-9. doi: 10.1016/j.bbrc.2011.12.104. Epub 2011 Dec 27.
Because the expression of EBNA1 is prevalent in all EBV-associated tumors, it has become one of the most attractive drug targets for the discovery of anti-EBV compounds. In a cell-based reporter system, EBNA1 consistently upregulated the transcription of an oriP-Luc mini-EBV episome by 6- to 8-fold. The treatment of cells with 50 μM EGCG effectively blocked the binding of EBNA1 to oriP-DNA both in vivo and in vitro, which led to the abrogation of EBNA1-dependent episome maintenance and transcriptional enhancement. Importantly, the anti-EBNA1 effects caused by EGCG ultimately impaired the persistence of EBV latent infection. Our data suggest that the inhibition of EBNA1 activity by EGCG could be a promising starting point for the development of new protocols for anti-EBV therapy.
由于 EBNA1 的表达普遍存在于所有 EBV 相关肿瘤中，因此它已成为发现抗 EBV 化合物的最有吸引力的药物靶点之一。在基于细胞的报告系统中，EBNA1 始终将 oriP-Luc 微型 EBV episome 的转录上调 6-8 倍。用 50 μM EGCG 处理细胞可有效阻止 EBNA1 在体内和体外与 oriP-DNA 的结合，从而导致 EBNA1 依赖性 episome 维持和转录增强的中断。重要的是，EGCG 引起的抗 EBNA1 作用最终损害了 EBV 潜伏感染的持续存在。我们的数据表明，EGCG 抑制 EBNA1 活性可能是开发新的 EBV 治疗方案的有前途的起点。
