Arginine methylation is a post-translational modification that is implicated in multiple biological functions including transcriptional regulation. The expression of protein arginine methyltransferases (PRMT) has been shown to be upregulated in various cancers. PRMTs have emerged as attractive targets for the development of new cancer therapies. Here, we describe the identification of a natural compound, licochalcone A, as a novel, reversible and selective inhibitor of PRMT6. Since expression of PRMT6 is upregulated in human breast cancers and is associated with oncogenesis, we used the human breast cancer cell line system to study the effect of licochalcone A treatment on PRMT6 activity, cell viability, cell cycle, and apoptosis. We demonstrated that licochalcone A is a non-S-adenosyl L-methionine (SAM) binding site competitive inhibitor of PRMT6. In MCF-7 cells, it inhibited PRMT6-dependent methylation of histone H3 at arginine 2 (H3R2), which resulted in a significant repression of estrogen receptor activity. Licochalcone A exhibited cytotoxicity towards human MCF-7 breast cancer cells, but not MCF-10A human breast epithelial cells, by upregulating p53 expression and blocking cell cycle progression at G2/M, followed by apoptosis. Thus, licochalcone A has potential for further development as a therapeutic agent against breast cancer.
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Research Article|
November 27 2020
Licochalcone A is a Natural Selective Inhibitor of Arginine Methyltransferase 6
Shuai Gong;
Shuai Gong
Zhengzhou University, Zhengzhou, China
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Shinji Maegawa;
Shinji Maegawa
MD Anderson Cancer Center, Houston, Texas, United States
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Yanwen Yang;
Yanwen Yang
MD Anderson Cancer Center, Houston, Texas, United States
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Vidya Gopalakrishnan;
Vidya Gopalakrishnan
MD Anderson Cancer Center, Houston, Texas, United States
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Guangrong Zheng;
Guangrong Zheng
College of Pharmacy, University of Florida, Gainesville, Florida, United States
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Donghang Cheng
University of Texas M.D Anderson Cancer Center, Houston, Texas, United States
* Corresponding Author; email: dcheng@mdanderson.org
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Biochem J (2020) BCJ20200411.
Article history
Received:
May 19 2020
Revision Received:
November 16 2020
Accepted:
November 27 2020
Citation
Shuai Gong, Shinji Maegawa, Yanwen Yang, Vidya Gopalakrishnan, Guangrong Zheng, Donghang Cheng; Licochalcone A is a Natural Selective Inhibitor of Arginine Methyltransferase 6
. Biochem J 2020; BCJ20200411. doi: https://doi.org/10.1042/BCJ20200411Download citation file:
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