Daphnoretin, a novel protein kinase C activator, induces growth arrest irreversibly on Human Hepatoma HepG2 Cells

Abstract

Daphnoretin, a dicoumarin type natural product originally isolated from plant Wikstroemia indica C. A. Mey has been shown as a protein kinase C (PKC) activator with novel structure. Previous studies demonstrated that daphnoretin treatment inhibited the expression of hepatitis B virus surface antigen (HBsAg) in human hepatoma Hep3B cells. In this study, we found that daphnoretin inhibited cell growth and induced a G1‐phase cell cycle arrest in human hepatoma HepG2 cells. Treatment of HepG2 cells with daphnoretin significantly up‐regulated the expression of p21cip1 and decreased the kinase activity but not the protein levels of cdk2/cyclin E complex in HepG2 cells. Unlike the reversible effect of phobol ester, a well known protein kinase C activator, 48 hour‐treatment of daphnoretin caused an irreversible growth arrest in HepG2 cells associated with persistent accumulation of p21 in HepG2 cells. The transcriptome and miRNA expression profile analysis indicates that daphnoretin may coordinately regulate a set of growth related genes at transcriptional and miRNA mediated translational level in cultured HepG2 cells.