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- Title
Sanguinarine inhibits epithelial–mesenchymal transition via targeting HIF-1α/TGF-β feed-forward loop in hepatocellular carcinoma.
- Authors
Su, Qi; Fan, Mengying; Wang, Jingjing; Ullah, Asmat; Ghauri, Mohsin Ahmad; Dai, Bingling; Zhan, Yingzhuan; Zhang, Dongdong; Zhang, Yanmin
- Abstract
Epithelial–mesenchymal transition (EMT) plays a crucial role in hepatocellular carcinoma (HCC) progression. Hypoxia and excessive transforming growth factor-β (TGF-β) have been identified as inducers and target for EMT in HCC. Here, we show hypoxia inducible factor-1α (HIF-1α) and TGF-β form a feed-forward loop to induce EMT in HCC cells. Further mechanistic study indicates under both hypoxia and TGF-β stimulation, Smad and PI3K-AKT pathways are activated. We show sanguinarine, a natural benzophenanthridine alkaloid, impairs the proliferation of nine kinds of HCC cell lines and the colony formation of HCC cells. In hypoxic and TGF-β cell models, sanguinarine inhibits HIF-1α signaling and the expression of EMT markers, translocation of Snail and activation of both Smad and PI3K-AKT pathways. Sanguinarine could also inhibit TGF-β-induced cell migration in HCC cells. In vivo studies reveal that the administration of sanguinarine inhibits tumor growth and HIF-1α signaling, inhibits the expression changes of EMT markers as well as Smad and PI3K-AKT pathway proteins. Our findings suggest that sanguinarine is a promising candidate targeting HIF-1α/TGF-β signaling to improve the treatment for HCC patients.
- Publication
Cell Death & Disease, 2019, Vol 10, Issue 12, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-019-2173-1