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

Tsui-Hwa Tseng; Huei-Jane Lee; Yean-Jang Lee; Ko-Chao Lee; Chien-Heng Shen; Hsing-Chun Kuo

doi:10.3390/biomedicines9091110

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

Biomedicines. 2021 Aug 30;9(9):1110. doi: 10.3390/biomedicines9091110.

Authors

Tsui-Hwa Tseng^{1

2}, Huei-Jane Lee³, Yean-Jang Lee⁴, Ko-Chao Lee⁵, Chien-Heng Shen⁶, Hsing-Chun Kuo^{7

8

9

10}

Affiliations

¹ Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung 40201, Taiwan.
² Department of Medical Education, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
³ Department of Biochemistry, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
⁴ Department of Chemistry, National Changhua University of Education, Changhua 50007, Taiwan.
⁵ Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
⁶ Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
⁷ Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi 61363, Taiwan.
⁸ Research Fellow, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
⁹ Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan.
¹⁰ Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi 61363, 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.

Keywords: Ailanthoidol; TGF-β1; anti-hepatic cancer progression; p-38MAPK.