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The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation

The deregulation of the Wnt/β-catenin signaling pathway is a central event in colorectal cancer progression, thus a promising target for drug development. Many natural compounds, such as flavonoids, have been described as Wnt/β-catenin inhibitors and consequently modulate important biological proces...

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Autores principales: Predes, Danilo, Oliveira, Luiz F. S., Ferreira, Laís S. S., Maia, Lorena A., Delou, João M. A., Faletti, Anderson, Oliveira, Igor, Amado, Nathalia G., Reis, Alice H., Fraga, Carlos A. M., Kuster, Ricardo, Mendes, Fabio A., Borges, Helena L., Abreu, Jose G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966512/
https://www.ncbi.nlm.nih.gov/pubmed/31817828
http://dx.doi.org/10.3390/cancers11121968
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author Predes, Danilo
Oliveira, Luiz F. S.
Ferreira, Laís S. S.
Maia, Lorena A.
Delou, João M. A.
Faletti, Anderson
Oliveira, Igor
Amado, Nathalia G.
Reis, Alice H.
Fraga, Carlos A. M.
Kuster, Ricardo
Mendes, Fabio A.
Borges, Helena L.
Abreu, Jose G.
author_facet Predes, Danilo
Oliveira, Luiz F. S.
Ferreira, Laís S. S.
Maia, Lorena A.
Delou, João M. A.
Faletti, Anderson
Oliveira, Igor
Amado, Nathalia G.
Reis, Alice H.
Fraga, Carlos A. M.
Kuster, Ricardo
Mendes, Fabio A.
Borges, Helena L.
Abreu, Jose G.
author_sort Predes, Danilo
collection PubMed
description The deregulation of the Wnt/β-catenin signaling pathway is a central event in colorectal cancer progression, thus a promising target for drug development. Many natural compounds, such as flavonoids, have been described as Wnt/β-catenin inhibitors and consequently modulate important biological processes like inflammation, redox balance, cancer promotion and progress, as well as cancer cell death. In this context, we identified the chalcone lonchocarpin isolated from Lonchocarpus sericeus as a Wnt/β-catenin pathway inhibitor, both in vitro and in vivo. Lonchocarpin impairs β-catenin nuclear localization and also inhibits the constitutively active form of TCF4, dnTCF4-VP16. Xenopus laevis embryology assays suggest that lonchocarpin acts at the transcriptional level. Additionally, we described lonchocarpin inhibitory effects on cell migration and cell proliferation on HCT116, SW480, and DLD-1 colorectal cancer cell lines, without any detectable effects on the non-tumoral intestinal cell line IEC-6. Moreover, lonchocarpin reduces tumor proliferation on the colorectal cancer AOM/DSS mice model. Taken together, our results support lonchocarpin as a novel Wnt/β-catenin inhibitor compound that impairs colorectal cancer cell growth in vitro and in vivo.
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spelling pubmed-69665122020-01-27 The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation Predes, Danilo Oliveira, Luiz F. S. Ferreira, Laís S. S. Maia, Lorena A. Delou, João M. A. Faletti, Anderson Oliveira, Igor Amado, Nathalia G. Reis, Alice H. Fraga, Carlos A. M. Kuster, Ricardo Mendes, Fabio A. Borges, Helena L. Abreu, Jose G. Cancers (Basel) Article The deregulation of the Wnt/β-catenin signaling pathway is a central event in colorectal cancer progression, thus a promising target for drug development. Many natural compounds, such as flavonoids, have been described as Wnt/β-catenin inhibitors and consequently modulate important biological processes like inflammation, redox balance, cancer promotion and progress, as well as cancer cell death. In this context, we identified the chalcone lonchocarpin isolated from Lonchocarpus sericeus as a Wnt/β-catenin pathway inhibitor, both in vitro and in vivo. Lonchocarpin impairs β-catenin nuclear localization and also inhibits the constitutively active form of TCF4, dnTCF4-VP16. Xenopus laevis embryology assays suggest that lonchocarpin acts at the transcriptional level. Additionally, we described lonchocarpin inhibitory effects on cell migration and cell proliferation on HCT116, SW480, and DLD-1 colorectal cancer cell lines, without any detectable effects on the non-tumoral intestinal cell line IEC-6. Moreover, lonchocarpin reduces tumor proliferation on the colorectal cancer AOM/DSS mice model. Taken together, our results support lonchocarpin as a novel Wnt/β-catenin inhibitor compound that impairs colorectal cancer cell growth in vitro and in vivo. MDPI 2019-12-07 /pmc/articles/PMC6966512/ /pubmed/31817828 http://dx.doi.org/10.3390/cancers11121968 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Predes, Danilo
Oliveira, Luiz F. S.
Ferreira, Laís S. S.
Maia, Lorena A.
Delou, João M. A.
Faletti, Anderson
Oliveira, Igor
Amado, Nathalia G.
Reis, Alice H.
Fraga, Carlos A. M.
Kuster, Ricardo
Mendes, Fabio A.
Borges, Helena L.
Abreu, Jose G.
The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation
title The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation
title_full The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation
title_fullStr The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation
title_full_unstemmed The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation
title_short The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation
title_sort chalcone lonchocarpin inhibits wnt/β-catenin signaling and suppresses colorectal cancer proliferation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966512/
https://www.ncbi.nlm.nih.gov/pubmed/31817828
http://dx.doi.org/10.3390/cancers11121968
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