Ailanthoidol, a Neolignan, Suppresses TGF-β1-Induced HepG2 Hepatoblastoma Cell Progression.

Ailanthoidol (ATD), a neolignan, possessed an antitumor promotion effect in the mouse skin model in our previous investigation. However, other antitumor properties remain to be elucidated. Liver cancer is a major cause of death in the world, and its prognosis and survival rate are poor. Therefore, the prevention and therapy of liver cancer have received much attention. TGF (transforming growth factor)-β1, a cytokine, plays a critical role in the progression of liver cancer. This study determined the inhibitory effects of ATD on the migration and invasion induced by TGF-β1 in HepG2 hepatoblastoma cells. Furthermore, ATD reduced the TGF-β1-promoted colony number of HepG2 hepatoblastoma cells. In addition to reversing TGF-β1-induced cell scattering, ATD suppressed TGF-β1-induced expression of integrin α3, vimentin, N-cadherin, and matrix metalloproteinase 2 (MMP2). Finally, this study found that ATD significantly inhibited TGF-β1-promoted phosphorylation of p-38 mitogen-activated protein kinase (MAPK) and Smad 2. Furthermore, the administration of SB203580 (p38MAPK inhibitor) suppressed TGF-β1-induced expression of integrin α3, N-cadherin, and MMP2. These results demonstrate a novel mechanism of ATD against progression of liver cancer.