Mycoepoxydiene induces apoptosis and inhibits TPA-induced invasion in human cholangiocarcinoma cells via blocking NF-κB pathway.
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.
The First Affiliated Hospital of Xiamen University, Xiamen 361003, China; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361003, China.
Wenjiao
W
Li
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361003, China.
Ming
M
Li
The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Xinhui
X
Su
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361003, China.
Liping
L
Qin
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361003, China.
Mengmeng
M
Miao
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361003, China.
Chundong
C
Yu
School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Yuemao
Y
Shen
The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. Electronic address: luoqi@medmail.com.cn.
Qi
Q
Luo
The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. Electronic address: qiangch88@gmail.com.
Qiang
Q
Chen
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D011753:Pyrones / Q000494:pharmacology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects
C554292:12-O-tetradecanoylphorbol-1,3-acetate; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D016328:NF-kappa B; D011753:Pyrones; C476085:mycoepoxydiene; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate
Apoptosis; Cholangiocarcinoma; Invasion; Mycoepoxydiene; NF-κB