Antioxidant and anticancer activity of Artemisia princeps var.orientalis extract in HepG2 and Hep3B hepatocellular carcinoma cells

Objective：The aim of the present study was to investigate antioxidant and the anticancerigen activity of a methanol extract from Artemisia princeps var.orientalis （APME）,a well-known traditional herbal medicine in Asia,in hepatocellular cancer cells.Methods：To evaluate the antioxidant activity of APME,reactive oxygen species （ROS） and the antioxidant enzymes,superoxide dismutase （SOD） and catalase were investigated in HepG2 cells exposed to APME （5,100,and 200 μg/mL） for 72 h.Then,to evaluate the anticancer activity of APME,we investigated the proliferation and apoptosis induction of HepG2 and Hep3B cells exposed to APME （1-200 μg/mL） for 24,48,and 72 h.Results：APME dose-dependently reduced the generation of ROS in the presence of H2O2 compared with control cells.Furthermore,it increased catalase and SOD activity.Moreover,APME inhibited cell proliferation in a dose-and time-dependcnt manner,but at concentrations lower than 100 μg/mL,the inhibition was less dose-dependent than time-dependent.HepG2 and Hep3B cells exposed to 5,100,and 200 μg/mL APME for 72 h underwent cell cycle arrest and apoptosis.Exposure to APME resulted in a significant increase in the number of cells in G1 phase and a decrease in the G2/M phase cell population.In addition,APME induced P53 expression of HepG2 cells in a dose-dependent manner,and played a role in the downregulation of Bcl-2 and upregulation of Bax in both HepG2 and Hep3B cells.Conclusions：These results indicate the potential role of APME as an antioxidant and anticancerigen agent in hepatocarcinoma cell lines.

Artemiprincepsolides A-F,Novel Germacrane-guaiane and Eudesmane-guaiane Sesquiterpenoid Dimers from Artemisia princeps and Their Antihepatoma Activity

Artemiprincepsolides A-F(1-6)were isolated from Artemisia princeps guided by bioactivity and elucidated by comprehensive spectral data and ECD calculation.Compounds 1-3 represented the first connecting model of germacrane-guaiane hetero-dimeric adducts,and compounds 4-6 were eudesmane-guaiane hetero-coupled sesquiterpenoid dimers,meanwhile,all these were presumably formed by Diels-Alder cycloaddition.Compounds 1-6 were evaluated for their hepatomatic cytotoxicity on three hepatoma cell lines,and demonstrated cytotoxicity with IC_(50)values in the range of 5.0-67.3μmol/L.Interestingly,compound 1 manifested significant cytotoxicity against HepG2,Huh7,and SK-Hep-1 cells with IC_(50)values of 9.9,9.2,and 5.0μmol/L,which were almost equivalent to the positive control,sorafenib.Flow cytometry data and Western blot assays revealed the most active compound 1 dose-dependently inhibited cell migration and invasion,and significantly induced HepG2 cells arrest in G2/M phase by downregulating proteins pcdc2 and upregulating the level of protein CyclinB1;and induced apoptosis by downregulating of Bcl-2 expression and upregulating Bax level.