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

Autor: Wang L; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Deng K; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Gong L; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Zhou L; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Sayed S; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Li H; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Sun Q; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Su Z; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Wang Z; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Liu S; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Zhu H; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Cancer Research Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, China., Song J; 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., Lu D; 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.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2020 Sep; Vol. 159, pp. 104955. Date of Electronic Publication: 2020 May 30.
DOI: 10.1016/j.phrs.2020.104955
Abstrakt: 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 APC min/+ 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.
(Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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