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Mycoepoxydiene induces apoptosis and inhibits TPA-induced invasion in human cholangiocarcinoma cells via blocking NF-κB pathway
Li W.1; Li M.1; Su X.1; Qin L.1; Miao M.1; Yu C.1; Shen Y.2; Luo Q.1; Chen Q.1
2014
Source PublicationBiochimie
ISSN61831638 03009084
Volume101Issue:1Pages:183-191
Abstract

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 anti-apoptotic proteins such as Bcl-X and Bcl-2, two targets of NF-κB. 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-κB activation via blocking phosphorylation and degradation of IκBα and phosphorylation of IκB kinase (IKK). MED had no effect on the activation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK) 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. © 2014 Elsevier Masson SAS. All rights reserved.

KeywordApoptosis Cholangiocarcinoma Invasion Mycoepoxydiene Nf-κb
DOI10.1016/j.biochi.2014.01.012
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000336109600020
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被引频次[WOS]:7   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Faculty of Health Sciences
Affiliation1.Xiamen University
2.Shandong University
3.National Institute of Diabetes and Digestive and Kidney Diseases
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Li W.,Li M.,Su X.,et al. Mycoepoxydiene induces apoptosis and inhibits TPA-induced invasion in human cholangiocarcinoma cells via blocking NF-κB pathway[J]. Biochimie,2014,101(1):183-191.
APA Li W..,Li M..,Su X..,Qin L..,Miao M..,...&Chen Q..(2014).Mycoepoxydiene induces apoptosis and inhibits TPA-induced invasion in human cholangiocarcinoma cells via blocking NF-κB pathway.Biochimie,101(1),183-191.
MLA Li W.,et al."Mycoepoxydiene induces apoptosis and inhibits TPA-induced invasion in human cholangiocarcinoma cells via blocking NF-κB pathway".Biochimie 101.1(2014):183-191.
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