Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling

Abstract The bioflavonoid apigenin has been shown to possess cancer-preventive and anti-cancer activities. In a drug screening, we found that apigenin can inhibit Wnt/β-catenin signaling, a pathway that participates in pivotal biological functions, which dis-regulation results in various human disea...

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Autores principales:	Chung-Ming Lin, Hsin-Han Chen, Chun-An Lin, Hui-Chung Wu, Jim Jinn-Chyuan Sheu, Hui-Jye Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a3f49179f4840959ec4a17293cc46c9
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spelling	oai:doaj.org-article:7a3f49179f4840959ec4a17293cc46c92021-12-02T15:05:05ZApigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling10.1038/s41598-017-00409-z2045-2322https://doaj.org/article/7a3f49179f4840959ec4a17293cc46c92017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00409-zhttps://doaj.org/toc/2045-2322Abstract The bioflavonoid apigenin has been shown to possess cancer-preventive and anti-cancer activities. In a drug screening, we found that apigenin can inhibit Wnt/β-catenin signaling, a pathway that participates in pivotal biological functions, which dis-regulation results in various human diseases including cancers. However, the underlying mechanism of apigenin in this pathway and its link to anti-cancer activities remain largely unknown. Here we showed that apigenin reduced the amount of total, cytoplasmic, and nuclear β-catenin, leading to the suppression in the β-catenin/TCF-mediated transcriptional activity, the expression of Wnt target genes, and cell proliferation of Wnt-stimulated P19 cells and Wnt-driven colorectal cancer cells. Western blotting and immunofluorescent staining analyses further revealed that apigenin could induce autophagy-mediated down-regulation of β-catenin in treated cells. Treatment with autophagy inhibitors wortmannin and chloroquine compromised this effect, substantiating the involvement of autophagy-lysosomal system on the degradation of β-catenin during Wnt signaling through inhibition of the AKT/mTOR signaling pathway. Our data not only pointed out a route for the inhibition of canonical Wnt signaling through the induction of autophagy-lysosomal degradation of key player β-catenin, but also suggested that apigenin or other treatments which can initiate this degradation event are potentially used for the therapy of Wnt-related diseases including cancers.Chung-Ming LinHsin-Han ChenChun-An LinHui-Chung WuJim Jinn-Chyuan SheuHui-Jye ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chung-Ming Lin Hsin-Han Chen Chun-An Lin Hui-Chung Wu Jim Jinn-Chyuan Sheu Hui-Jye Chen Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling
description	Abstract The bioflavonoid apigenin has been shown to possess cancer-preventive and anti-cancer activities. In a drug screening, we found that apigenin can inhibit Wnt/β-catenin signaling, a pathway that participates in pivotal biological functions, which dis-regulation results in various human diseases including cancers. However, the underlying mechanism of apigenin in this pathway and its link to anti-cancer activities remain largely unknown. Here we showed that apigenin reduced the amount of total, cytoplasmic, and nuclear β-catenin, leading to the suppression in the β-catenin/TCF-mediated transcriptional activity, the expression of Wnt target genes, and cell proliferation of Wnt-stimulated P19 cells and Wnt-driven colorectal cancer cells. Western blotting and immunofluorescent staining analyses further revealed that apigenin could induce autophagy-mediated down-regulation of β-catenin in treated cells. Treatment with autophagy inhibitors wortmannin and chloroquine compromised this effect, substantiating the involvement of autophagy-lysosomal system on the degradation of β-catenin during Wnt signaling through inhibition of the AKT/mTOR signaling pathway. Our data not only pointed out a route for the inhibition of canonical Wnt signaling through the induction of autophagy-lysosomal degradation of key player β-catenin, but also suggested that apigenin or other treatments which can initiate this degradation event are potentially used for the therapy of Wnt-related diseases including cancers.
format	article
author	Chung-Ming Lin Hsin-Han Chen Chun-An Lin Hui-Chung Wu Jim Jinn-Chyuan Sheu Hui-Jye Chen
author_facet	Chung-Ming Lin Hsin-Han Chen Chun-An Lin Hui-Chung Wu Jim Jinn-Chyuan Sheu Hui-Jye Chen
author_sort	Chung-Ming Lin
title	Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling
title_short	Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling
title_full	Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling
title_fullStr	Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling
title_full_unstemmed	Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling
title_sort	apigenin-induced lysosomal degradation of β-catenin in wnt/β-catenin signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7a3f49179f4840959ec4a17293cc46c9
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Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling

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