Mycoepoxydiene induces apoptosis and inhibits TPA-induced invasion in human cholangiocarcinoma cells via blocking NF-κB pathway.

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-XL 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.

• Authors: Wenjiao Li, Ming Li, Xinhui Su, Liping Qin, Mengmeng Miao, Chundong Yu, Yuemao Shen, Qi Luo, Qiang Chen
• Journal: Biochimie (Biochimie) Vol. 101 Pg. 183-91 (Jun 2014) ISSN: 1638-6183 [Electronic] France
• PMID: 24486723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• 12-O-tetradecanoylphorbol-1,3-acetate
• Antineoplastic Agents
• Bridged-Ring Compounds
• NF-kappa B
• Pyrones
• mycoepoxydiene
• MMP9 protein, human
• Matrix Metalloproteinase 9
• Tetradecanoylphorbol Acetate

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Bile Duct Neoplasms (drug therapy, pathology)
• Bile Ducts, Intrahepatic (pathology)
• Bridged-Ring Compounds (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Cholangiocarcinoma (drug therapy, pathology)
• Drug Screening Assays, Antitumor
• Humans
• Inhibitory Concentration 50
• Matrix Metalloproteinase 9 (genetics, metabolism)
• NF-kappa B (metabolism)
• Neoplasm Invasiveness
• Promoter Regions, Genetic
• Pyrones (pharmacology)
• Signal Transduction
• Tetradecanoylphorbol Acetate (analogs & derivatives, pharmacology)
• Transcriptional Activation (drug effects)