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Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells

The naturally occurring isothiocyanate sulforaphane (SFN) from cruciferous vegetables is associated with growth inhibition of various cancer types, including colorectal cancer. Colorectal cancer is most frequently driven by hyperactive Wnt/β-catenin signaling. Here, we show that SFN treatment reduce...

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Autores principales: Bernkopf, Dominic B., Daum, Gabriele, Brückner, Martina, Behrens, Jürgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188060/
https://www.ncbi.nlm.nih.gov/pubmed/30338040
http://dx.doi.org/10.18632/oncotarget.26125
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author Bernkopf, Dominic B.
Daum, Gabriele
Brückner, Martina
Behrens, Jürgen
author_facet Bernkopf, Dominic B.
Daum, Gabriele
Brückner, Martina
Behrens, Jürgen
author_sort Bernkopf, Dominic B.
collection PubMed
description The naturally occurring isothiocyanate sulforaphane (SFN) from cruciferous vegetables is associated with growth inhibition of various cancer types, including colorectal cancer. Colorectal cancer is most frequently driven by hyperactive Wnt/β-catenin signaling. Here, we show that SFN treatment reduced growth of three unrelated colorectal cancer cell lines (SW480, DLD1 and HCT116) via induction of cell death and inhibition of proliferation. Importantly, SFN inhibits Wnt/β-catenin signaling in colorectal cancer cells as shown by inhibition of β-catenin-dependent luciferase reporters and repression of β-catenin target genes (AXIN2, LGR5). SFN inhibits Wnt signaling downstream of β-catenin degradation and induces the formation of nuclear β-catenin structures associated with closed chromatin. Co-expression of the transcription factors LEF1 or TCF4 prevented formation of these structures and rescued inhibition of Wnt/β-catenin signaling by SFN. Our findings provide a molecular basis explaining SFN effects in colorectal cancer cells and underline its potential for prevention and therapy of colorectal cancer.
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spelling pubmed-61880602018-10-18 Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells Bernkopf, Dominic B. Daum, Gabriele Brückner, Martina Behrens, Jürgen Oncotarget Research Paper The naturally occurring isothiocyanate sulforaphane (SFN) from cruciferous vegetables is associated with growth inhibition of various cancer types, including colorectal cancer. Colorectal cancer is most frequently driven by hyperactive Wnt/β-catenin signaling. Here, we show that SFN treatment reduced growth of three unrelated colorectal cancer cell lines (SW480, DLD1 and HCT116) via induction of cell death and inhibition of proliferation. Importantly, SFN inhibits Wnt/β-catenin signaling in colorectal cancer cells as shown by inhibition of β-catenin-dependent luciferase reporters and repression of β-catenin target genes (AXIN2, LGR5). SFN inhibits Wnt signaling downstream of β-catenin degradation and induces the formation of nuclear β-catenin structures associated with closed chromatin. Co-expression of the transcription factors LEF1 or TCF4 prevented formation of these structures and rescued inhibition of Wnt/β-catenin signaling by SFN. Our findings provide a molecular basis explaining SFN effects in colorectal cancer cells and underline its potential for prevention and therapy of colorectal cancer. Impact Journals LLC 2018-09-21 /pmc/articles/PMC6188060/ /pubmed/30338040 http://dx.doi.org/10.18632/oncotarget.26125 Text en Copyright: © 2018 Bernkopf et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Bernkopf, Dominic B.
Daum, Gabriele
Brückner, Martina
Behrens, Jürgen
Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells
title Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells
title_full Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells
title_fullStr Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells
title_full_unstemmed Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells
title_short Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells
title_sort sulforaphane inhibits growth and blocks wnt/β-catenin signaling of colorectal cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188060/
https://www.ncbi.nlm.nih.gov/pubmed/30338040
http://dx.doi.org/10.18632/oncotarget.26125
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