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XB-ART-49632
J Biol Chem December 19, 2014; 289 (51): 35456-67.
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Isoquercitrin suppresses colon cancer cell growth in vitro by targeting the Wnt/β-catenin signaling pathway.

Amado NG , Predes D , Fonseca BF , Cerqueira DM , Reis AH , Dudenhoeffer AC , Borges HL , Mendes FA , Abreu JG .


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.

PubMed ID: 25359775
PMC ID: PMC4271231
Article link: J Biol Chem


Species referenced: Xenopus
Genes referenced: cat.2 chrd.1 ctnnb1 dld egr2 foxg1 hoxb9 lef1 lrp6 nodal nodal1 nodal3.1 nodal3.2 otx2 pcna ren sia1 tbxt ventx1.2 wnt3a wnt8a

Disease Ontology terms: colon cancer

Article Images: [+] show captions
References [+] :
Abreu, Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. 2002, Pubmed, Xenbase