Identification of a new class of WNT1 inhibitor: Cancer cells migration, G-quadruplex stabilization and target validation

Lien Cheng Chang, Tsung Chih Chen, Shiag Jiun Chen, Chun Liang Chen, Chia Chung Lee, Shih Hsiung Wu, Yun Yen, Hsu Shan Huang, Jing Jer Lin

研究成果: 雜誌貢獻文章同行評審

4 引文 斯高帕斯(Scopus)

摘要

Developing the Wnt pathway inhibitors has been considered as a therapeutic approach for cancers and other Wnt-related diseases. Previously we found that the G-rich sequence of WNT1 promoter is capable of forming G-quadruplex structure and stabilizing agents for Wnt1-mediated signaling pathway. Using a established cell-based drug screen system that enabled the evaluation of WNT1 expression activity in a G-quadruplex structure dependent manner, we evaluated a series of 6-substituted 9-chloro-11H-indeno[1,2-c]quinolin-11-one derivatives that potentially inhibit the Wnt1-mediated signaling pathway. The most potent compound SJ26 showed repression of WNT1 activity in a G-quadruplex structure-dependent manner. Moreover, compound SJ26 inhibited the WNT1-mediated downstream signaling pathway and suppressed migration activity of cancer cells. Thus, we have identified a tetracyclic azafluorenone, SJ26, that is capable of binding to G-quadruplex DNA structure, repressing WNT1 expression, and inhibiting cell migration.
原文英語
頁(從 - 到)67986-68001
頁數16
期刊Oncotarget
7
發行號42
DOIs
出版狀態已發佈 - 十月 18 2016

ASJC Scopus subject areas

  • 腫瘤科

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