当前位置:首页 > 科研成果 > 本所论文
论文题目: Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2-dependent cancer
作者: Chen Huiming, Gao Shijuan, Li Jiandong, Liu Dong, Sheng Chunjie, Yao Chen, Jiang Wei, Wu Jiaoxiang, Chen Shuai*, and Huang Wenlin*.
联系作者:
刊物名称: Oncotarget
期:
卷:
页:
年份: 2015
影响因子: 6.368
论文下载: 下载地址
摘要: Polycomb repressive complex 2 (PRC2), which is responsible for the trimethylation of H3K27 (H3K27me3), plays a part in tumorigenesis, development and/or maintenance of adult tissue specificity. The pivotal role of PRC2 in cancer makes it a therapeutic target for epigenetic cancer therapy. However, natural compounds targeting the enhancer of zeste homolog 2 (EZH2) - embryonic ectoderm development (EED) interaction to disable PRC2 complex are scarcely reported. Here, we reported the screening and identification of natural compounds which could disrupt the EZH2-EED interaction. One of these compounds, wedelolactone, binds to EED with a high affinity (KD = 2.82 muM), blocks the EZH2-EED interaction in vitro, induces the degradation of PRC2 core components and modulates the expression of detected PRC2 downstream targets and cancer-related genes. Furthermore, some PRC2-dependent cancer cells undergone growth arrest upon treatment with wedelolactone. Thus, wedelolactone and its derivatives which target the EZH2-EED interaction could be candidates for the treatment of PRC2-dependent cancer.