Discovery of a chemical compound that suppresses expression of BEX2, a dormant cancer stem cell-related protein

Satoshi Saijoh, Mao Nakamura-Shima, Rie Shibuya-Takahashi, Ryo Ito, Akira Sugawara, Tomoko Yamazaki, Takayuki Imai, Yukinori Asada, Kazuto Matsuura, Wataru Iwai, Yuta Wakui, Makoto Abue, Sadafumi Kawamura, Yu Katayose, Haruna Fujimori, Mai Mochizuki, Jun Yasuda, Kazunori Yamaguchi, Kazuo Sugamura, Kennichi SatohYukio Katori, Keiichi Tamai

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer stem cells (CSCs) are believed to cause cancer metastasis and recurrence. BEX2 (brain expressed X-linked gene 2) is a CSC-related gene that is expressed in dormant CSCs in cholangiocarcinoma and induces resistance against chemotherapy. The aim of the present study was to identify small compounds that have activity to inhibit BEX2 expression and result in the attenuation of CSC-related phenotypes. We screened 9600 small chemical compounds in high-throughput screening using cholangiocarcinoma cell line HuCCT1 expressing BEX2 protein fused with NanoLuc, and identified a compound, BMPP (1, 3-Benzenediol, [4-(4-methoxyphenyl)-1H-pyrazol-3-yl]). BMPP was found to exert decreasing effects on BEX2 protein expression and G0 phase population of the tumor cells, and increasing effects on ATP levels and chemotherapeutic sensitivity of the cells. These findings indicate that BMPP is a valuable chemical compound for reducing dormant CSC-related phenotypes. Thus, the identification of BMPP as a potential CSC suppressor provides scope for the development of novel therapeutic modalities for the treatment of cancers with BEX2 overexpressing CSCs.

Original languageEnglish
Pages (from-to)132-139
Number of pages8
JournalBiochemical and biophysical research communications
Volume537
DOIs
Publication statusPublished - 2021 Jan 22
Externally publishedYes

Keywords

  • BEX2
  • Cholangiocarcinoma
  • Dormant cancer stem cell
  • Hepatocellular carcinoma

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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