TY - JOUR
T1 - Discovery of a chemical compound that suppresses expression of BEX2, a dormant cancer stem cell-related protein
AU - Saijoh, Satoshi
AU - Nakamura-Shima, Mao
AU - Shibuya-Takahashi, Rie
AU - Ito, Ryo
AU - Sugawara, Akira
AU - Yamazaki, Tomoko
AU - Imai, Takayuki
AU - Asada, Yukinori
AU - Matsuura, Kazuto
AU - Iwai, Wataru
AU - Wakui, Yuta
AU - Abue, Makoto
AU - Kawamura, Sadafumi
AU - Katayose, Yu
AU - Fujimori, Haruna
AU - Mochizuki, Mai
AU - Yasuda, Jun
AU - Yamaguchi, Kazunori
AU - Sugamura, Kazuo
AU - Satoh, Kennichi
AU - Katori, Yukio
AU - Tamai, Keiichi
N1 - Funding Information:
This research was supported in part by JSPS KAKENHI grant numbers JP: 19K08430 , 19K17416 , 18K15799 , 16K07132 , 17K11166 , 20K17068 , 20H03756 , and 18H02368 and Practical Research for Innovative Cancer Control from AMED by grant number JP17ck0106197 , and Takeda Medical Foundation .
Publisher Copyright:
© 2020
PY - 2021/1/22
Y1 - 2021/1/22
N2 - 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.
AB - 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.
KW - BEX2
KW - Cholangiocarcinoma
KW - Dormant cancer stem cell
KW - Hepatocellular carcinoma
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U2 - 10.1016/j.bbrc.2020.11.022
DO - 10.1016/j.bbrc.2020.11.022
M3 - Article
C2 - 33412384
AN - SCOPUS:85098870601
SN - 0006-291X
VL - 537
SP - 132
EP - 139
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -
