Inhibition of invasion by N-trans-feruloyloctopamine via AKT,p38MAPK and EMT related signals in hepatocellular carcinoma cells |
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Authors: | Zhong-Tian Bai Zheng-Rong Wu Li-Li Xi Xun Li Peng Chen Fu-Qiang Wang Wen-Bo Meng Wen-Ce Zhou Xin-An Wu Xiao-Jun Yao Min Zhang |
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Institution: | 1. The Second Department of General Surgery, The First Hospital of Lanzhou University, Key Laboratory of Biotherapy and Regenerative Medicine, Gansu Province, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, Gansu, China;2. School of Pharmacy, Lanzhou University, Lanzhou 730020, China;3. Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China;4. Department of Chemistry, Lanzhou University, Lanzhou 730000, China;5. Gansu Provincial Hospital, Lanzhou 730000, China |
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Abstract: | 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. |
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Keywords: | AKT MAPK E-cadherin Epithelial to mesenchymal transition (EMT) Hepatocellular carcinoma |
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