Article ID Journal Published Year Pages File Type
5527192 Experimental Cell Research 2017 18 Pages PDF
Abstract

•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.

Graphical abstractDownload high-res image (148KB)Download full-size image

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
Authors
, , , , , ,