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Cytotoxic activity of bromodomain inhibitor NVS-CECR2-1 on human cancer cells
- Title
- Cytotoxic activity of bromodomain inhibitor NVS-CECR2-1 on human cancer cells
- Authors
- Park S.G.; Lee D.; Seo H.-R.; Lee S.-A.; Kwon J.
- Ewha Authors
- 권종범
- SCOPUS Author ID
- 권종범
- Issue Date
- 2020
- Journal Title
- Scientific Reports
- ISSN
- 2045-2322
- Citation
- Scientific Reports vol. 10, no. 1
- Publisher
- Nature Research
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Bromodomain (BRD), a protein module that recognizes acetylated lysine residues on histones and other proteins, has recently emerged as a promising therapeutic target for human diseases such as cancer. While most of the studies have been focused on inhibitors against BRDs of the bromo- and extra-terminal domain (BET) family proteins, non-BET family BRD inhibitors remain largely unexplored. Here, we investigated a potential anticancer activity of the recently developed non-BET family BRD inhibitor NVS-CECR2-1 that targets the cat eye syndrome chromosome region, candidate 2 (CECR2). We show that NVS-CECR2-1 inhibits chromatin binding of CECR2 BRD and displaces CECR2 from chromatin within cells. NVS-CECR2-1 exhibits cytotoxic activity against various human cancer cells, killing SW48 colon cancer cells in particular with a submicromolar half maximum inhibition value mainly by inducing apoptosis. The sensitivity of the cancer cells to NVS-CECR2-1 is reduced by CECR2 depletion, suggesting that NVS-CECR2-1 exerts its activity by targeting CECR2. Interestingly, our data show that NVS-CECR2-1 also kills cancer cells by CECR2-independent mechanism. This study reports for the first time the cancer cell cytotoxic activity for NVS-CECR2-1 and provides a possibility of this BRD inhibitor to be developed as an anticancer therapeutic agent. © 2020, The Author(s).
- DOI
- 10.1038/s41598-020-73500-7
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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