| Autor: |
Fonseca BF; Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil., Predes D; Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil., Cerqueira DM; Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil., Reis AH; Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil., Amado NG; Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil., Cayres MC; Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil., Kuster RM; Universidade Federal do Rio de Janeiro, Instituto de Pesquisas em Produtos Naturais, Rio de Janeiro, Brazil., Oliveira FL; Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil., Mendes FA; Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil., Abreu JG; Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil. |
| Abstrakt: |
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. |
