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Ailanthoidol, a Neolignan, Suppresses TGF-β1-Induced HepG2 Hepatoblastoma Cell Progression
Tsui-Hwa Tseng1,2, Huei-Jane Lee3, Yean-Jang Lee4
1Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung 40201, Taiwan.
Abstract:
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.
Insights
Ailanthoidol (ATD) inhibits liver cancer progression by blocking cell migration and invasion. This neolignan also reduces colony formation and key protein expressions linked to cancer spread, offering a potential new therapy.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Liver cancer poses a significant global health challenge with poor survival rates.
- Transforming growth factor-beta 1 (TGF-β1) is a critical cytokine implicated in liver cancer progression.
- Ailanthoidol (ATD), a neolignan, has previously shown antitumor promotion effects.
Purpose of the Study:
- To investigate the inhibitory effects of ATD on TGF-β1-induced liver cancer cell progression.
- To elucidate the molecular mechanisms underlying ATD's anti-cancer properties in HepG2 cells.
Main Methods:
- HepG2 hepatoblastoma cells were treated with ATD and TGF-β1.
- Cell migration, invasion, and colony formation assays were performed.
- Expression levels of key proteins (integrin α3, vimentin, N-cadherin, MMP2) and phosphorylation of signaling molecules (p38 MAPK, Smad 2) were analyzed.
Main Results:
- ATD significantly inhibited TGF-β1-induced migration, invasion, and colony formation of HepG2 cells.
- ATD reversed TGF-β1-induced cell scattering and suppressed the expression of integrin α3, vimentin, N-cadherin, and MMP2.
- ATD inhibited TGF-β1-induced phosphorylation of p38 MAPK and Smad 2, with p38 MAPK inhibition further reducing key protein expressions.
Conclusions:
- ATD demonstrates potent inhibitory effects against TGF-β1-induced liver cancer cell progression.
- ATD acts through the inhibition of p38 MAPK and Smad 2 signaling pathways.
- These findings suggest ATD as a potential therapeutic agent for liver cancer treatment.
