期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 27, 期 4, 页码 989-993出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2016.12.073
关键词
N-trans-feruloyloctopamine (FO); AKT; MAPK; E-cadherin; Epithelial to mesenchymal transition (EMT); Hepatocellular carcinoma
资金
- Gansu Province Science Foundation for Distinguished Young Scholars [1606RJDA317]
- Health Industry Research Project of Gansu Province [GWGL2014-45]
- Science and Technology Program of Lanzhou City [2015-3-93]
- National Natural Science Fund of China [31270543, 31570509]
- Natural Science Foundation of Gansu Province [1208RJZA219, 1606RJZA159, 1606RJZA087]
N-trans-feruloyloctopamine (FO) isolated from Garlic skin was identified as the primary antioxidant constituents, however, the effect of which on HCC invasion is still unclear. Herein, the FO was synthesized and its antitumor activities were evaluated in HCC cell lines. Cellular functional analyses have revealed that the reformed FO owns strong abilities of inhibiting cell proliferation and invasion in HCC cells. Molecular data have further showed that FO could significantly decrease the phosphorylation levels of Akt and p38 MAPK. In addition, the expression of Slug was inhibited and the level of E-cadherin increased. Molecular docking analysis indicates that the H-bond and hydrophobic interactions were critical for FO and E-cadherin binding, but FO did not seem to act directly on phosphorylated Akt and p38 MAPK. We have thus concluded that reformed FO inhibits cell invasion might be directly through EMT related signals (E-cadherin) and indirectly through PI3K/Akt, p38 MAPK signaling pathways. FO might be a promising drug in HCC treatment and prognosis. (C) 2017 Elsevier Ltd. All rights reserved.
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