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.