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

Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling.
Author Information (click to view)

Lin CM, Chen HH, Lin CA, Wu HC, Sheu JJ, Chen HJ,


Lin CM, Chen HH, Lin CA, Wu HC, Sheu JJ, Chen HJ, (click to view)

Lin CM, Chen HH, Lin CA, Wu HC, Sheu JJ, Chen HJ,

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Scientific reports 2017 03 237(1) 372 doi 10.1038/s41598-017-00409-z
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.

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