Derricin and derricidin inhibit Wnt/β-catenin signaling and suppress colon cancer cell growth in vitro

PloS One
Barbara F FonsecaJose G Abreu

Abstract

Overactivation of the Wnt/β-catenin pathway in adult tissues has been implicated in many diseases, such as colorectal cancer. Finding chemical substances that can prevent this phenomenon is an emerging problem. Recently, several natural compounds have been described as Wnt/β-catenin inhibitors and might be promising agents for the control of carcinogenesis. Here, we describe two natural substances, derricin and derricidin, belonging to the chalcone subclass, that show potent transcriptional inhibition of the Wnt/β-catenin pathway. Both chalcones are able to affect the cell distribution of β-catenin, and inhibit Wnt-specific reporter activity in HCT116 cells and in Xenopus embryos. Derricin and derricidin also strongly inhibited canonical Wnt activity in vitro, and rescued the Wnt-induced double axis phenotype in Xenopus embryos. As a consequence of Wnt/β-catenin inhibition, derricin and derricidin treatments reduce cell viability and lead to cell cycle arrest in colorectal cancer cell lines. Taken together, our results strongly support these chalcones as novel negative modulators of the Wnt/β-catenin pathway and colon cancer cell growth in vitro.

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Citations

Jan 26, 2017·Protein Science : a Publication of the Protein Society·Freddi Huan Tran, Jie J Zheng
Dec 26, 2018·Journal of Drug Targeting·Dana ElkhalifaAshraf Khalil
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Feb 14, 2021·Biochemical and Biophysical Research Communications·Gabriela C SomainiCeleste Tríbulo
Jun 3, 2021·Cancers·Radka MichalkovaJan Mojzis

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Methods Mentioned

BETA
IEC-18
Assay
transfection
flow cytometry

Software Mentioned

WinMDI
GraphPad Prism
GraphPad
CellQuest

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