JIB-04, A Small Molecule Histone Demethylase Inhibitor, Selectively Targets Colorectal Cancer Stem Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway

Min Seong Kim, Hye In Cho, Hee Jung Yoon, Ye Hyeon Ahn, Eun Jung Park, Yan Hua Jin, Yeun Kyu Jang

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43 Citations (Scopus)


Although several epigenetic modulating drugs are suggested to target cancer stem cells (CSCs), additional identification of anti-CSC drugs is still necessary. Here we showed that JIB-04, a pan-selective inhibitor of histone demethylase(s), was identified as a small molecule that selectively target colorectal CSCs. Our data showed that JIB-04 is capable of reducing self-renewal and stemness of colorectal CSCs in three different colorectal cancer cell lines. JIB-04 significantly attenuated CSC tumorsphere formation, growth/relapse, invasion, and migration in vitro. Furthermore, JIB-04-treated colorectal cancer cells showed reduced tumorigenic activity in vivo. RNA sequencing analysis revealed that JIB-04 affected various cancer-related signaling pathways, especially Wnt/β-catenin signaling, which is crucial for the proliferation and maintenance of colorectal cancer cells. qRT-PCR and TOP/FOP flash luciferase assays showed that JIB-04 down-regulated the expression of Wnt/β-catenin-regulated target genes associated with colorectal CSC function. Overall, the effects of JIB-04 were equal to or greater than those of salinomycin, a known anti-colorectal CSC drug, despite the lower concentration of JIB-04 compared with that of salinomycin. Our results strongly suggest that JIB-04 is a promising drug candidate for colorectal cancer therapy.

Original languageEnglish
Article number6611
JournalScientific reports
Issue number1
Publication statusPublished - 2018 Dec 1

Bibliographical note

Funding Information:
The authors thank all faculty members in Department of Systems Biology for their encouragement. Specially, the authors thank JooHun Lee, Tae Ho Lee, In Kwon Chung, Jihyun F. Kim, Hyun-Soo Cho, and Kwang-Min Choe for key insights, support and helpful advice. This work was supported in part by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) [No. 2011-0030049] and partly by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and future Planning [No. 2016R1A2B1012050]. In addition, M.S.K., H.I.C., and Y.K.J. were supported in part by the Brain Korea 21 (BK21) PLUS program. In addition, this research was partly supported by National Natural Science Foundation of China (No. 81660494). This research was in part supported by the Graduate School of YONSEI University Research Scholarship Grants in 2017 (to H.I.C.).

Publisher Copyright:
© 2018 The Author(s).

All Science Journal Classification (ASJC) codes

  • General


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