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Title: The anti-cancer activity of an andrographolide analogue functions through a GSK-3β-independent Wnt/β-catenin signaling pathway in colorectal cancer cells
Authors: Somrudee Reabroi
Rungnapha Saeeng
Nittaya Boonmuen
Teerapich Kasemsuk
Witchuda Saengsawang
Kanoknetr Suksen
Weiming Zhu
Pawinee Piyachaturawat
Arthit Chairoungdua
Ocean University of China
Mahidol University
Burapha University
Keywords: Multidisciplinary
Issue Date: 1-Dec-2018
Citation: Scientific Reports. Vol.8, No.1 (2018)
Abstract: © 2018 The Author(s). The Wnt/β-catenin signaling pathway plays a key role in the progression of human colorectal cancers (CRCs) and is one of the leading targets of chemotherapy agents developed for CRC. The present study aimed to investigate the anti-cancer effects and molecular mechanisms of 19-O-triphenylmethyl andrographolide (RS-PP-050), an andrographolide analogue and determine its activity in the Wnt/β-catenin pathway. RS-PP-050 was found to potently inhibit the proliferation and survival of HT-29 CRC cells. It induces cell cycle arrest and promotes apoptotic cell death which was associated with the activation of PARP-1 and p53. Furthermore, RS-PP-050 exerts inhibitory effects on β-catenin transcription by suppressing T-cell factor/lymphocyte enhancer factor (TCF/LEF) activity in cells overexpressing β-catenin and by down-regulating the endogenous expression of Wnt target genes. RS-PP-050 also decreased the protein expression of the active form of β-catenin but functions independently of GSK-3β, a negative regulator of Wnt. Interestingly, RS-PP-050 extensively blocks phosphorylation at Ser675 of β-catenin which links to interference of the nuclear translocation of β-catenin and might contribute to Wnt inactivation. Collectively, our findings reveal the underlying anti-cancer mechanism of an andrographolide analogue and provide useful insight for exploiting a newly chemotherapeutic agent in Wnt/β-catenin-overexpressing CRC cells.
ISSN: 20452322
Appears in Collections:Scopus 2018

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