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

• Published in: International journal of molecular sciences 2018-05, Vol.19 (6), p.1556
• Main Authors: Xing, Shangping, Yu, Wenxia, Zhang, Xiaofeng, Luo, Yingyi, Lei, Zhouxi, Huang, Dandan, Lin, Ji, Huang, Yuechun, Huang, Shaowei, Nong, Feifei, Zhou, Chunhua, Wei, Gang
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Biomarkers, Tumor - metabolism; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemical compounds; Cytotoxicity; Dendrobium - chemistry; Dendrobium officinale; Epithelial-Mesenchymal Transition - drug effects; epithelial–mesenchymal transition (EMT); Flavonoids - isolation & purification; Flavonoids - pharmacology; Flavonoids - therapeutic use; Glycosides; Growth factors; Hepatocellular carcinoma; hepatocellular carcinoma (HCC) cells; Hepatocytes; Herbal medicine; High-performance liquid chromatography; Humans; Invasiveness; isoviolanthin; Liver; Liver cancer; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Mesenchyme; Metalloproteinase; Metastases; Models, Biological; Neoplasm Invasiveness; NMR; Nuclear magnetic resonance; Pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Physicochemical properties; PI3K/Akt/mTOR; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Smad protein; Smad Proteins - metabolism; structural identification; TGF-β/Smad; TOR protein; TOR Serine-Threonine Kinases - metabolism; Transforming growth factor; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19061556

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 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.