Chlorquinaldol targets the beta-catenin and T-cell factor 4 complex and exerts anti-colorectal cancer activity
Chlorquinaldol targets the beta-catenin and T-cell factor 4 complex and exerts anti-colorectal cancer activity
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氯喹那多靶向 β-连环蛋白和 T 细胞因子 4 复合物并发挥抗结直肠癌活性
DOI：
10.1016/j.phrs.2020.104955
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发表时间：
2020
影响因子：
9.3
通讯作者：
Lu Desheng
中科院分区：
文献类型：
--
作者：
Wang Ling;Deng Ke;Gong Liang;Zhou Liang;Sayed Sapna;Li Huan;Sun Qi;Su Zijie;Wang Zhongyuan;Liu Shanshan;Zhu Huifang;Song Jiaxing;Lu Desheng
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.
