Cytotoxic activity of bromodomain inhibitor NVS-CECR2-1 on human cancer cells

Seul Gi Park, Daye Lee, Hye Ran Seo, Shin Ai Lee, Jongbum Kwon

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Article number16330
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2020

Bibliographical note

Funding Information:
This work was supported by grants 2015M2A2A7A01041767, 2018R1A2B2007128 and 2019R1A5A6099645 from the National Research Foundation of Korea.

Publisher Copyright:
© 2020, The Author(s).

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