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The Histone Lysine-specific Demethylase 1 Inhibitor, SP2509 Exerts Cytotoxic Effects against Renal Cancer Cells through Downregulation of Bcl-2 and Mcl-1

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Author(s)
Kaixin WuSeon Min WooTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Journal of Cancer Prevention
Issued Date
2020
Volume
25
Issue
2
Keyword
KDM1ASP2509Bcl-2Mcl-1Apoptosis
Abstract
Lysine-specific histone demethylase 1 (LSD1), also known as KDM1A, can remove the methyl group from lysine 4 and 9 at histone H3, which regulates transcriptional suppression and activation. Recently, high expression of LSD1 in tumors has been shown to be involved in cancer cell proliferation, metastasis, and poor prognosis. We found that SP2509, a potent and reversible inhibitor of LSD1, induced apoptosis in human renal carcinoma (Caki and ACHN) and glioma (U87MG) cells. Pharmacological inhibition and siRNA-mediated silencing of LSD1 expression effectively downregulated anti-apoptotic proteins such as Bcl-2 and Mcl-1. Ectopic expression of these proteins markedly attenuated SP2509-induced apoptosis. At a mechanistic level, we found that inhibition of LSD1 downregulated Bcl-2 at a transcriptional level. Interestingly, protein expression of Mcl-1 was modulated at a post-translation level. Our results reveal that LSD1 could induce apoptotic cell death in renal carcinoma cells through downregulation of Bcl-2 and Mcl-1.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Citation
Kaixin Wu et al. (2020). The Histone Lysine-specific Demethylase 1 Inhibitor, SP2509 Exerts Cytotoxic Effects against Renal Cancer Cells through Downregulation of Bcl-2 and Mcl-1. Journal of Cancer Prevention, 25(2), 79–86. doi: 10.15430/JCP.2020.25.2.79
Type
Article
ISSN
2288-3657
Source
http://www.jcpjournal.org/journal/view.html?pn=vol&uid=836&vmd=Full
DOI
10.15430/JCP.2020.25.2.79
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43137
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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