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BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus

BHX (N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide), a Wnt signaling pathway inhibitor, effectively inhibits tumor cell growth, but the underlying mechanism is unclear. Thus, we aim to investigate the effects and associated mechanism of BHX action on A549 and MCF-7 cell l...

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Autores principales: Ding, Fengxia, Wang, Meisa, Du, Yibo, Du, Shuangshuang, Zhu, Zhongling, Yan, Zhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133598/
https://www.ncbi.nlm.nih.gov/pubmed/27910912
http://dx.doi.org/10.1038/srep38331
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author Ding, Fengxia
Wang, Meisa
Du, Yibo
Du, Shuangshuang
Zhu, Zhongling
Yan, Zhao
author_facet Ding, Fengxia
Wang, Meisa
Du, Yibo
Du, Shuangshuang
Zhu, Zhongling
Yan, Zhao
author_sort Ding, Fengxia
collection PubMed
description BHX (N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide), a Wnt signaling pathway inhibitor, effectively inhibits tumor cell growth, but the underlying mechanism is unclear. Thus, we aim to investigate the effects and associated mechanism of BHX action on A549 and MCF-7 cell lines. In our study, MTT(3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) and xenograft model assay indicated that cell growth was inhibited by BHX at a range of concentrations in vitro and in vivo. The expression of β-catenin and Wnt signaling pathway downstream target genes were decreased evidently under BHX treatment. Flow cytometry also revealed that BHX treatment significantly induced G1 arrest. Further analysis showed that BHX lowered the transcriptional level of β-catenin. In conclusion, BHX inhibited the nuclear synthesis of β-catenin, thereby suppressing the Wnt signaling pathway and further inhibiting tumor growth and proliferation.
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spelling pubmed-51335982017-01-27 BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus Ding, Fengxia Wang, Meisa Du, Yibo Du, Shuangshuang Zhu, Zhongling Yan, Zhao Sci Rep Article BHX (N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide), a Wnt signaling pathway inhibitor, effectively inhibits tumor cell growth, but the underlying mechanism is unclear. Thus, we aim to investigate the effects and associated mechanism of BHX action on A549 and MCF-7 cell lines. In our study, MTT(3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) and xenograft model assay indicated that cell growth was inhibited by BHX at a range of concentrations in vitro and in vivo. The expression of β-catenin and Wnt signaling pathway downstream target genes were decreased evidently under BHX treatment. Flow cytometry also revealed that BHX treatment significantly induced G1 arrest. Further analysis showed that BHX lowered the transcriptional level of β-catenin. In conclusion, BHX inhibited the nuclear synthesis of β-catenin, thereby suppressing the Wnt signaling pathway and further inhibiting tumor growth and proliferation. Nature Publishing Group 2016-12-02 /pmc/articles/PMC5133598/ /pubmed/27910912 http://dx.doi.org/10.1038/srep38331 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ding, Fengxia
Wang, Meisa
Du, Yibo
Du, Shuangshuang
Zhu, Zhongling
Yan, Zhao
BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus
title BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus
title_full BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus
title_fullStr BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus
title_full_unstemmed BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus
title_short BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus
title_sort bhx inhibits the wnt signaling pathway by suppressing β-catenin transcription in the nucleus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133598/
https://www.ncbi.nlm.nih.gov/pubmed/27910912
http://dx.doi.org/10.1038/srep38331
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