Title:Effects of Natural Compounds on Xenopus Embryogenesis: A Potential Read Out for Functional Drug Discovery Targeting Wnt/β-catenin Signaling
VOLUME: 12 ISSUE: 19
Author(s):Nathalia G. Amado, Barbara F. Fonseca, Debora Malta Cerqueira, Alice H. Reis, Alessandro Bolis Costa Simas, Ricardo Machado Kuster, Fabio A. Mendes and Jose G. Abreu
Affiliation:Instituto de Ciencias Biomedicas, Programa de Biologia Celular e do Desenvolvimento, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude, bloco F sala 09, Ilha do Fundao - 21941-590 - Rio de Janeiro, RJ, Brazil.
Keywords:Flavonoids, Quercetin, Wnt, embryonic patterning, embryonic axis, rutin, polyposis coli, novel molecules, signaling pathways, phenotypes, neural tube defects.
Abstract:Maternal Wnt/β-Catenin signaling is essential to establish dorsal-specific gene expression required for
axial patterning in Xenopus. Deregulation of this pathway causes axis phenotypes in frog embryos. In adult life, mutations
in the Wnt pathway components are associated with many diseases, such as polyposis coli; osteoporosispseudoglioma
syndrome (OPPG); skeletal dysplasia; neural tube defects, cancer and many others. Thus, a better understanding
of Wnt/β-catenin signaling will have great and significant impact on Biology and Medicine. In this aspect,
natural compounds are potential targets as novel molecules that could modulate the Wnt pathway. For instance, flavonoids
are a large group of natural compounds found in plants that modulate important cellular and molecular mechanisms
related to diseases, but the specific in vivo mechanism of action of most flavonoids remain unknown. In this way,
Xenopus embryos may provide an efficient model, since it is frequently used to test and identify the role of molecules that
affect Wnt/β-catenin signaling. Here, we describe a combination of approaches to outline and characterize the role of
two flavonoids, quercetin and rutin, on Wnt/β-catenin signaling, using Xenopus embryos as an experimental model.
Our data support that quercetin is potential in vivo modulator of canonical Wnt signaling and that this effect might depend
on the structure of this molecule, as we did not observe any effect with rutin treatment, a flavonol structurally-related to
quercetin. This model is useful to analyze effects of quercetin and other flavonoids in vivo and to provide further understanding
of how natural compounds can modulate signaling pathways, using Xenopus embryos as a fast and efficient reading
of in vivo effects of those compounds.