Mycoepoxydiene induces apoptosis and inhibits TPA-induced invasion in human cholangiocarcinoma cells via blocking NF-kappa B pathway
- 医学院－已发表论文 
Human cholangiocarcinoma (CCA) is a chemoresistant bile duct carcinoma with a poor prognosis. Conventional chemotherapy and radiotherapy have not been reported to be effective in improving long-term survival. Mycoepoxydiene (MED), a polyketide isolated from the marine fungal strain Diaporthe sp. HLY-1 associated with mangroves, has been shown to be an agent capable of inducing apoptosis in MCF-7 and Hela cell lines. However, little is known about the effect of MED in CCA. Herein, we investigated the effect of MED on CCA cells proliferation and invasion. The results demonstrated that MED induced apoptosis in CCA cells such as SK-ChA-1 and Mz-ChA-1 through inhibiting the expression of antiapoptotic proteins such as BcI-XL and Bcl-2, two targets of NF-KB. In addition, MED significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced CCA cells invasion in a dose-dependent manner by reducing the expression of matrix metalloelastase 9 (MMP-9). Moreover, MED inhibited TPA-induced NF-KB activation via blocking phosphorylation and degradation of hcBct and phosphorylation of IKB kinase (IKK). MED had no effect on the activation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (INK) and p38, which are also involved in regulating the MMP-9 expression. Collectively, MED significantly suppressed proliferation and invasion of CCA cells such as SK-ChA-1 and Mz-ChA-1, suggesting that MED is a potential lead compound for the development of novel drugs for therapy of CCA. (C) 2014 Elsevier Masson SAS. All rights reserved.