Isoquercitrin suppresses colon cancer cell growth in vitro by targeting the Wnt/β-Catenin signaling pathway

Nathália G. Amado, Danilo Predes, Barbara F. Fonseca, Débora M. Cerqueira, Alice H. Reis, Ana C. Dudenhoeffer, Helena L. Borges, Fábio A. Mendes, Jose G. Abreu

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Flavonoids are plant-derived polyphenolic molecules that have potential biological effects including anti-oxidative, antiinflammatory, anti-viral, and anti-tumoral effects. These effects are related to the ability of flavonoids to modulate signaling pathways, such as the canonical Wnt signaling pathway. This pathway controls many aspects of embryonic development and tissue maintenance and has been found to be deregulated in a range of human cancers. We performed several in vivo assays in Xenopus embryos, a functional model of canonical Wnt signaling studies, and also used in vitro models, to investigate whether isoquercitrin affects Wnt/β-catenin signaling. Our data provide strong support for an inhibitory effect of isoquercitrin on Wnt/ β-catenin, where the flavonoid acts downstream of β-catenin translocation to the nuclei. Isoquercitrin affects Xenopus axis establishment, reverses double axes and the LiCl hyperdorsalization phenotype, and reduces Xnr3 expression. In addition, this flavonoid shows anti-tumoral effects on colon cancer cells (SW480, DLD-1, and HCT116), whereas exerting no significant effect on non-tumor colon cell (IEC-18), suggesting a specific effect in tumor cells in vitro. Taken together, our data indicate that isoquercitrin is an inhibitor of Wnt/β-catenin and should be further investigated as a potential novel anti-tumoral agent.

Original languageEnglish
Pages (from-to)35456-35457
Number of pages2
JournalJournal of Biological Chemistry
Volume289
Issue number51
DOIs
StatePublished - 19 Dec 2014
Externally publishedYes

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