2. Academic Validation
  3. Chlorquinaldol targets the β-catenin and T-cell factor 4 complex and exerts anti-colorectal cancer activity

Chlorquinaldol targets the β-catenin and T-cell factor 4 complex and exerts anti-colorectal cancer activity

  • Pharmacol Res. 2020 Sep;159:104955. doi: 10.1016/j.phrs.2020.104955.
Ling Wang 1,  Ke Deng 1,  Liang Gong 1,  Liang Zhou 1,  Sapna Sayed 1,  Huan Li 1,  Qi Sun 1,  Zijie Su 1,  Zhongyuan Wang 1,  Shanshan Liu 1,  Huifang Zhu 1,  Jiaxing Song 2,  Desheng Lu 3
Affiliations

Affiliations

  • 1 Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China.
  • 2 Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China. Electronic address: jxsong@szu.edu.cn.
  • 3 Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China. Electronic address: delu@szu.edu.cn.
PMID: 32485279 DOI: 10.1016/j.phrs.2020.104955
Abstract

Aberrant activation of Wnt signaling plays a critical role in the initiation and progression of colorectal Cancer (CRC). Chlorquinaldol (CQD) is a topical antimicrobial agent used to treat skin infections. Little is known about the Anticancer activity of CQD and its underlying mechanisms. In this study, CQD was demonstrated to inhibit Wnt/β-catenin signaling through targeting the downstream part of this pathway. The results showed that CQD could inhibit the acetylation of β-catenin and disrupt the interaction of β-catenin with T-cell factor 4 (TCF4), leading to reduced binding of β-catenin to the promoters of Wnt target genes and downregulation of the expression of these target genes. Moreover, treatment with CQD suppressed the proliferation, migration, invasion and stemness of CRC cells. In APCmin/+ mice and CRC cell xenografts, administration of CQD suppressed tumor growth and the expression of Wnt target genes c-Myc and Leucine-rich G protein-coupled receptor-5 (LGR5). These results strongly suggest that CQD may be a promising therapeutic agent in the treatment of CRC.

Keywords

8-Hydroxyquinoline; Colorectal cancer stem cell; Transcriptional regulation; Wnt/β-catenin signaling; β-catenin acetylation.

Figures
Products
Inhibitors & Agonists
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z