Dihydromyricetin induces mouse hepatoma Hepal-6 cell apoptosis via the transforming growth factor-β pathway.

Abstract

Dihydromyricetin (DHM) is a flavonoid compound which possesses potent antitumor activity. In the present study, it was demonstrated that DHM significantly inhibited proliferation and induced apoptosis in mouse hepatocellular carcinoma Hepal-6 cells. Transforming growth factor β (TGF-β) is recognized as a major profibrogenic cytokine and is therefore a common target for drugs in the treatment of liver disease. The present study aimed to investigate whether TGF-β was involved in DHM-triggered cell-viability inhibition and apoptosis induction. An MTT assay was used to evaluate the viability of Hepal-6 cells following DHM treatment. TGF-β signalling is mediated by Smads and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a crucial regulator of reactive oxygen species ROS production. TGF-β, Smad3, phosphorylated (p)-Smad2/3 and NOX4 protein expression levels were evaluated by western blot analysis. TGF-β and NOX4 gene expression levels were determined by quantitative polymerase chain reaction. The results indicated that DHM downregulated TGF-β, Smad3, p-Smad2/3 and NOX4 in a concentration-dependent manner. A cell counting assay indicated that DHM also inhibited Hepal-6 cell growth in a concentration-dependent manner. TGF-β expression was significantly decreased following DHM treatment. In conclusion, the results of the present study defined and supported a novel function for DHM, indicating that it induced cell apoptosis by downregulating ROS production via the TGF-β/Smad3 signaling pathway in mouse hepatocellular carcinoma Hepal-6 cells.