Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2-dependent cancer.

Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2-dependent cancer.

Oncotarget (2015-05-07)

Huiming Chen, Shijuan Gao, Jiandong Li, Dong Liu, Chunjie Sheng, Chen Yao, Wei Jiang, Jiaoxiang Wu, Shuai Chen, Wenlin Huang

PMID25944687

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.

MATERIALS

Product Number

Brand

Product Description

L6026

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62862

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