title: Isoquercitrin suppresses colon cancer cell growth in vitro by targeting the Wnt/β-catenin signaling pathway.
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.
authors.affiliation: From the Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21949-590, Brazil.
authors.forename: Nathália G
authors.initials: NG
authors.lastname: Amado
authors.affiliation: From the Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21949-590, Brazil.
authors.forename: Danilo
authors.initials: D
authors.lastname: Predes
authors.affiliation: From the Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21949-590, Brazil.
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Fonseca
authors.affiliation: From the Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21949-590, Brazil.
authors.forename: Débora M
authors.initials: DM
authors.lastname: Cerqueira
authors.affiliation: From the Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21949-590, Brazil.
authors.forename: Alice H
authors.initials: AH
authors.lastname: Reis
authors.affiliation: From the Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21949-590, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Dudenhoeffer
authors.affiliation: From the Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21949-590, Brazil.
authors.forename: Helena L
authors.initials: HL
authors.lastname: Borges
authors.affiliation: From the Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21949-590, Brazil.
authors.forename: Fábio A
authors.initials: FA
authors.lastname: Mendes
authors.affiliation: From the Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21949-590, Brazil garciajr@icb.ufrj.br.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Abreu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D051767:Early Growth Response Protein 2 / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018021:Lithium Chloride / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000235:genetics; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051767:Early Growth Response Protein 2; D029867:Xenopus Proteins; D051176:beta Catenin; C016527:isoquercitrin; D011794:Quercetin; D018021:Lithium Chloride
keywords: Colon Cancer; Flavonoid; Quercetin; Wnt Signaling; Xenopus; β-Catenin (B-Catenin)