کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5527192 | 1401569 | 2017 | 18 صفحه PDF | دانلود رایگان |

- Morin induced cytotoxicity in cultured HepG2 cells.
- Morin activated hippo pathway via Mst1 activation in transfected HepG2 cells.
- Morin suppressed Wnt/β-catenin signaling and induced G0/G1 cell cycle arrest.
- Morin inhibited NF-κB signaling through Mst1 activation in transfected HepG2 cells.
- Morin potentiates apoptosis through Mst1-JNK-caspase mediated mechanism in HepG2 cells.
Recent clinical and experimental evidences strongly acclaim Yes-associated protein (Yap), a key oncogenic driver in liver carcinogenesis, as a therapeutic target. Of the known multiple schemes to inhibit Yap activity, activation of Mammalian Sterile 20-like Kinase 1 (Mst1), an upstream regulator of Yap, appears to be a promising one. In this study, we hypothesize that morin, a bioflavonoid, mediates its anti-cancer effect through the activation of Mst1/hippo signaling in liver cancer cells. To test this hypothesis, both full length Mst1 (F-Mst1) and kinase active N-terminal Mst1 (N-Mst1)-overexpressed HepG2 cells were used. Exposure of F-Mst1 overexpressed HepG2 cells to morin activated Mst1 by caspase-3 cleavage and thereby inhibited Yap nuclear translocation and fostered apoptosis. Morin suppressed NF-κB p65 and Wnt/β-catenin signaling through Mst1 activation via cleavage and phosphorylation, leading to cell death. Annexin-V/PI staining further confirmed the induction of apoptosis in morin treated F-Mst1 overexpressed cells. The present study shows that morin targets cell survival molecules such as NF-κB p65 and β-catenin through activation of hippo signaling. Therefore, morin could be considered as a potential anti-cancer agent against liver cancer.
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Journal: Experimental Cell Research - Volume 355, Issue 2, 15 June 2017, Pages 124-141