Open AccessDerricin and Derricidin Inhibit Wnt/β-Catenin Signaling and Suppress Colon Cancer Cell Growth In Vitro
Author(s) -
Bárbara F. Fonseca,
Danilo Predes,
Débora M. Cerqueira,
Alice H. Reis,
Nathália G. Amado,
Marina C. L. Cayres,
Ricardo Machado Kuster,
Felipe Leite de Oliveira,
Fábio A. Mendes,
José G. Abreu
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0120919
Subject(s) - wnt signaling pathway , xenopus , catenin , biology , carcinogenesis , colorectal cancer , microbiology and biotechnology , cell growth , cancer research , chalcone , viability assay , cell cycle , lrp6 , chemistry , cell , cancer , signal transduction , biochemistry , genetics , gene , stereochemistry
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 .