期刊
ONCOTARGET
卷 7, 期 42, 页码 67986-68001出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6622
关键词
Wnt1-mediated signaling pathway; G-quadruplex; 6-substituted 9-chloro-11H-indeno[1,2-c]quinolin-11-ones; reporter assay
资金
- Ministry of Science and Technology
- Taipei Medical University [NSC 101-2113-M-016-001, TMU102-AE1-B32, TMUTOP-103003, NSC 101-2311-B-002-020-MY3]
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.
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