Abstract：
:Dysregulation of the Wnt/β-catenin signaling pathway is involved in the development of human hepatocellular carcinoma and has thus emerged as a therapeutic target for this malignant tumor. In this study, we employed sensitive cell-based assays to identify aplykurodin A isolated from Aplysia kurodai as an antagonist of Wnt/β-catenin signaling. Aplykurodin A inhibited β-catenin responsive transcription, which was stimulated by a Wnt3a-conditioned medium or a glycogen synthase kinase 3β inhibitor by accelerating intracellular β-catenin degradation. Aplykurodin A downregulated the level of oncogenic β-catenin and decreased the expression of β-catenin-dependent gene, leading to inhibition of human hepatoma Hep3B and SNU475 cell proliferation. Moreover, apoptosis and autophagy were elicited by aplykurodin A, as indicated by an increase the number of Annexin V-FITC-stained cells and the formation of microtubule-associated protein 1 light chain 3 puncta, respectively, in Hep3B and SNU475 cells. Our findings suggest that aplykurodin A provides a novel therapeutic strategy for human hepatocellular carcinoma via stimulation of oncogenic β-catenin degradation.
journal_name
Mar Drugsjournal_title
Marine drugsauthors
Lee J,Zhou W,Na M,Oh Sdoi
10.3390/md18040210subject
Has Abstractpub_date
2020-04-13 00:00:00issue
4issn
1660-3397pii
md18040210journal_volume
18pub_type
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