Journal
ONCOTARGET
Volume 6, Issue 15, Pages 13049-13059Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3790
Keywords
epigenetic cancer therapy; surface plasmon resonance; cell cycle; apoptosis; cell migration
Categories
Funding
- National Basic Research Program of China (973 Program) [2012CB518900, 2011CB504706, 2011CB504805]
- National Natural Science Foundation of China [81171572]
- Guangdong Innovative Research Team Program [2009010058]
Ask authors/readers for more resources
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 mu M), 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available