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Aqueous extract of Sanguisorba officinalis blocks the Wnt/β-catenin signaling pathway in colorectal cancer cells

(the Chinese name is DiYu, DY) exerts significant anti-proliferative activities against colorectal cancer (CRC) cells. Since most of CRC result from the aberrant activation of the Wnt/β-catenin signaling pathway, inhibitors of the Wnt pathway are considered as promising anti-CRC agents. This study a...

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Bibliographic Details
Published in:RSC advances 2018-03, Vol.8 (19), p.10197-10206
Main Authors: Liu, Meng-Ping, Li, Wa, Dai, Cong, Kei Lam, Christopher Wai, Li, Zheng, Chen, Jie-Feng, Chen, Zuan-Guang, Zhang, Wei, Yao, Mei-Cun
Format: Article
Language:English
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Summary:(the Chinese name is DiYu, DY) exerts significant anti-proliferative activities against colorectal cancer (CRC) cells. Since most of CRC result from the aberrant activation of the Wnt/β-catenin signaling pathway, inhibitors of the Wnt pathway are considered as promising anti-CRC agents. This study aimed to investigate whether DY could be a potential herbal Wnt inhibitor, and the bioactive constituents and underlying molecular mechanisms for DY's inhibiting activities would be studied as well. Accordingly, the inhibitory activities of DY and its main components against the Wnt pathway were assessed using the single-luciferase reporter assay based on HEK293 cells. Additionally, the levels of key Wnt-related genes or proteins were measured to verify the inhibitory effects on the Wnt pathway of CRC cells. Finally, the underlying mechanisms accounting for the efficacy of candidate drugs were explored by the transcriptomic study. Results show that DY and its tannins (RZ), and saponins (ZG) significantly inhibited the Wnt pathway of HEK293 cells activated by wnt3a. However, their respective constituents were not effective as expected. Additionally, DY and RZ prominently down-regulated the levels of β-catenin and Wnt-targeted genes including , or of three CRC cells. Transcriptomic profiling study suggests that the down-regulation of the mRNA levels of Wnt-related genes such as may be associated with the inhibitory effects of DY and RZ on the Wnt pathway of HT29 cells. Therefore, our studies first uncovered the blocking activity of DY on the Wnt pathway, providing evidence for the rationale of developing Wnt inhibitors from DY as anti-CRC agents.
ISSN:2046-2069
2046-2069
DOI:10.1039/c8ra00438b