4.7 Article

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

Journal

BIOMEDICINES
Volume 9, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines9091110

Keywords

Ailanthoidol; TGF-beta 1; p-38MAPK; anti-hepatic cancer progression

Funding

  1. Ministry of Science and Technology Grant, Taiwan [MOST 108-2320-B-040-016-MY3, MOST 110-2320-B255-005-MY3]
  2. Ministry of Science and Technology
  3. Ministry of Education
  4. Chung Shan Medical University, Taiwan
  5. Chang Gung Memorial Hospital [CMRPG6J0151, CMRPG6J0152, CMRPG6J0153, ZRRPF6K0011]
  6. Chang Gung University of Science and Technology, Chia-Yi, Taiwan

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Ailanthoidol (ATD) exhibits anti-liver cancer properties by inhibiting TGF-beta 1-induced migration, invasion, and colony formation in HepG2 hepatoblastoma cells, as well as suppressing the expression of integrin alpha 3, vimentin, N-cadherin, and MMP2; it acts against liver cancer progression by inhibiting the phosphorylation of p-38 mitogen-activated protein kinase (MAPK) and Smad 2.
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)-beta 1, 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-beta 1 in HepG2 hepatoblastoma cells. Furthermore, ATD reduced the TGF-beta 1-promoted colony number of HepG2 hepatoblastoma cells. In addition to reversing TGF-beta 1-induced cell scattering, ATD suppressed TGF-beta 1-induced expression of integrin alpha 3, vimentin, N-cadherin, and matrix metalloproteinase 2 (MMP2). Finally, this study found that ATD significantly inhibited TGF-beta 1-promoted phosphorylation of p-38 mitogen-activated protein kinase (MAPK) and Smad 2. Furthermore, the administration of SB203580 (p38MAPK inhibitor) suppressed TGF-beta 1-induced expression of integrin alpha 3, N-cadherin, and MMP2. These results demonstrate a novel mechanism of ATD against progression of liver cancer.

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