Contrasting Effect of Curcumin on Hepatitis B Virus Replication According to the Hepatoma Cell Line

Abstract

In recent decades, considerable advances have been achieved in the treatmentof chronic hepatitis B. However, the currently available drugs have shortcomings. In thiscontext, several natural compounds have been proposed as potential agents to improveeither the outcome of antiviral treatment or the progression of chronic infection, withcurcumin being one of the most evaluated compounds due to its pleiotropic antiviralactivity. The aim of this study was to characterize the effect and mechanism of curcuminon hepatitis B virus (HBV) replication in two different experimental models. Treatment ofHepG22.15 and HBV-transfected Huh7 cells with curcumin revealed that the phytochemicaldifferentially modulated HBV replication in both cell lines. In HepG22.15 cells, the additionof curcumin had no effect on viral DNA, pregenomic RNA (pgRNA), and e antigen (HBeAg)levels, while it decreased Precore RNA and s antigen (HBsAg) levels. Conversely, in Huh-7cells, curcumin significantly increased viral progeny more than tenfold, as well as HBVRNAs and viral antigens. Furthermore, the analysis of the cellular mechanisms associatedwith the modulation of viral replication revealed that in Huh-7 cells, curcumin-induced cellcycle arrest in the G2/M phase and the modulation of genes involved in proliferation, cellcycle progression, and apoptosis, whereas no changes in cell cycle progression and geneexpression were observed in HepG22.15 cells. In conclusion, curcumin elicits a differentialcellular response in two hepatoma cell lines, which, in the case of Huh-7 cells, wouldprovide an optimal cellular setting that enhances HBV replication. Therefore, the antiviraleffect of this phytochemical remains controversial.