Abstract
Flavonoids are plant-derived polyphenolic molecules that have potential biological effects including anti-oxidative, anti-inflammatory, 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.
Highlights
Flavonoids are natural compounds capable of modulating signaling pathways in a variety of biological processes
Isoquercitrin Induces Axial Defects in Xenopus Embryos—Previous results from our group showed that the flavonoid isoquercitrin changes -catenin cellular localization in glioblastoma cells [15]
Four-cell-stage Xenopus embryos were treated with isoquercitrin (Fig. 1A) to investigate its function in affecting axis development
Summary
Flavonoids are natural compounds capable of modulating signaling pathways in a variety of biological processes. Our previous data have shown that isoquercitrin, which is derived from quercetin, affects the proliferation of glioblastoma cells, with lower toxicity [16] These anti-proliferative effects were accompanied by changes in -catenin cellular localization, suggesting that Wnt/-catenin signaling might be altered by this flavonoid [16]. Our data indicate that isoquercitrin acts as an inhibitor of Wnt/-catenin in Xenopus embryo experiments (in vivo) and in vitro and should be further investigated as a potential anti-tumoral agent.
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