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Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling.
- Source :
-
Scientific reports [Sci Rep] 2017 Mar 23; Vol. 7 (1), pp. 372. Date of Electronic Publication: 2017 Mar 23. - Publication Year :
- 2017
-
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.
- Subjects :
- Cell Line, Tumor
Cell Proliferation
Colorectal Neoplasms metabolism
Dishevelled Proteins metabolism
Humans
Low Density Lipoprotein Receptor-Related Protein-5 metabolism
Proto-Oncogene Proteins c-akt metabolism
TOR Serine-Threonine Kinases metabolism
Apigenin administration & dosage
Autophagy
Lysosomes metabolism
Wnt Signaling Pathway
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28337019
- Full Text :
- https://doi.org/10.1038/s41598-017-00409-z