RESUMEN

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/ß-catenin signaling. Our data provide strong support for an inhibitory effect of isoquercitrin on Wnt/ß-catenin, where the flavonoid acts downstream of ß-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/ß-catenin and should be further investigated as a potential novel anti-tumoral agent.

Asunto(s)

Proliferación Celular/efectos de los fármacos , Quercetina/análogos & derivados , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Western Blotting , Tipificación del Cuerpo/efectos de los fármacos , Tipificación del Cuerpo/genética , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Proteína 2 de la Respuesta de Crecimiento Precoz/genética , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/embriología , Embrión no Mamífero/metabolismo , Regulación del Desarrollo de la Expresión Génica , Células HCT116 , Humanos , Inmunohistoquímica , Hibridación in Situ , Cloruro de Litio/farmacología , Quercetina/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vía de Señalización Wnt/genética , Xenopus/embriología , Xenopus/genética , Xenopus/metabolismo , Proteínas de Xenopus/genética , beta Catenina/genética