Jiang Xiaoxin, Zeng Leping, Huang Jufang, Zhou Hui, Liu Yubin
The First Affiliated Hospital, University of South China, Hengyang, 421001, People's Republic of China.
Department of Anatomy and Neurobiology, Biology Postdoctoral Workstation, Basic School of Medicine Central South University, Changsha, 410013, People's Republic of China.
J Biochem Mol Toxicol. 2015 Oct;29(10):458-464. doi: 10.1002/jbt.21712. Epub 2015 Apr 28.
In this study, we explored the cytotoxic effects of arctigenin, a natural lignan compound, on human hepatocellular carcinoma (HCC) cells and check the involvement of phosphatidylinositol 3-kinase (PI3-K)/Akt signaling. HCC cells were treated with different concentrations of arctigenin and cell viability and apoptosis were assessed. Manipulating Akt signaling was used to determine its role in the action of arctigenin. Arctigenin significantly inhibited the viability of HCC cells in a concentration-dependent manner. Arctigenin induced apoptosis and activation of caspase-9 and -3. Overexpression of a constitutively active Akt mutant blocked arctigenin-induced apoptosis. Combinational treatment with arctigenin and the PI3-K inhibitor LY294002 significantly enhanced apoptosis. Arctigenin reduced the expression of Bcl-xL, Mcl-1, and survivin and the phosphorylation of mTOR and S6K, which were significantly reversed by overexpression of constitutively active Akt. This is the first report about the anticancer activity of arctigenin in HCC cells, which is mediated by inactivation of PI3-K/Akt signaling.
