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Int J Mol Sci. 2018 May 23;19(6). pii: E1556. doi: 10.3390/ijms19061556.

Isoviolanthin Extracted from Dendrobium officinale Reverses TGF-β1-Mediated Epithelial⁻Mesenchymal Transition in Hepatocellular Carcinoma Cells via Deactivating the TGF-β/Smad and PI3K/Akt/mTOR Signaling Pathways.

Author information

1
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. shopingxing@gmail.com.
2
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. yuwenxia3486@outlook.com.
3
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. zhangxiaofeng3486@outlook.com.
4
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. luoyingyi3486@outlook.com.
5
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. leizhouxi@outlook.com.
6
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. dandan3486@outlook.com.
7
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. linji88@gzucm.edu.cn.
8
The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China. huangyuechun3486@outlook.com.
9
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. shaoweihuang021@outlook.com.
10
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. feifeinong@outlook.com.
11
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. chunhuazhou021@outlook.com.
12
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. weigang021@outlook.com.

Abstract

Dendrobium officinale is a precious medicinal herb and health food, and its pharmacological actions have been studied and proved. However, the mechanisms by which its active flavonoid glycosides affect epithelial⁻mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells, such as HepG2 and Bel-7402 cells, have not been previously investigated. Therefore, we investigated whether isoviolanthin extracted from the leaves of Dendrobium officinale inhibits transforming growth factor (TGF)-β1-induced EMT in HCC cells. In this study, the physicochemical properties and structure of isoviolanthin were identified by HPLC, UV, ESIMS, and NMR and were compared with literature data. HCC cells were pretreated with 10 ng/mL TGF-β1 to induce EMT and then treated with isoviolanthin. Herein, we found that isoviolanthin exhibited no cytotoxic effects on normal liver LO2 cells but notably reduced the migratory and invasive capacities of TGF-β1-treated HCC cells. Additionally, isoviolanthin treatment decreased matrix metalloproteinase (MMP)-2 and -9 levels, and remarkably altered the expression of EMT markers via regulating the TGF-β/Smad and PI3K/Akt/mTOR signaling pathways; Western blot analysis confirmed that the effects of the inhibitors SB431542 and LY294002 were consistent with those of isoviolanthin. These findings demonstrate the potential of isoviolanthin as a therapeutic agent for the treatment of advanced-stage metastatic HCC.

KEYWORDS:

Dendrobium officinale; PI3K/Akt/mTOR; TGF-β/Smad; epithelial–mesenchymal transition (EMT); hepatocellular carcinoma (HCC) cells; isoviolanthin; structural identification

PMID:
29882900
PMCID:
PMC6032198
DOI:
10.3390/ijms19061556
[Indexed for MEDLINE]
Free PMC Article

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