本文采用的英格恩产品: 293T转染, Entranster-H, Entranster-H4000
Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2-dependent cancer
Huiming Chen 1 2 , Shijuan Gao 1 , Jiandong Li 1 , Dong Liu 1 , Chunjie Sheng 1 , Chen Yao 1 2 , Wei Jiang 1 , Jiaoxiang Wu 1 2 , Shuai Chen 1 3 , Wenlin Huang 1 3 4
- 1 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
- 2 School of Life Sciences, Anhui University, Hefei 230039, China.
- 3 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
- 4 The Key Laboratory of Tumor Targeted Medicine in Guangdong Province, Guangzhou Double Bio-product Inc., Guangzhou 510663, China.
Abstract
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 μM), 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.
Keywords: apoptosis; cell cycle; cell migration; epigenetic cancer therapy; surface plasmon resonance.