title: Derricin and derricidin inhibit Wnt/β-catenin signaling and suppress colon cancer cell growth in vitro.
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.
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Fonseca
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Danilo
authors.initials: D
authors.lastname: Predes
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Debora M
authors.initials: DM
authors.lastname: Cerqueira
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Alice H
authors.initials: AH
authors.lastname: Reis
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Nathalia G
authors.initials: NG
authors.lastname: Amado
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Marina C L
authors.initials: MC
authors.lastname: Cayres
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Pesquisas em Produtos Naturais, Rio de Janeiro, Brazil.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Kuster
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Felipe L
authors.initials: FL
authors.lastname: Oliveira
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Mendes
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Abreu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D045325:HCT116 Cells; D045782:Hemiterpenes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D060449:Wnt Signaling Pathway; D014981:Xenopus; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D005419:Flavonoids; D045782:Hemiterpenes; D051176:beta Catenin; C000598623:derricidin; C000604275:derricin