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Open Access Research article

Terminalia catappa attenuates urokinase-type plasminogen activator expression through Erk pathways in Hepatocellular carcinoma

Chao-Bin Yeh12, Yung-Luen Yu34, Chiao-Wen Lin5, Hui-Ling Chiou6, Ming-Ju Hsieh78* and Shun-Fa Yang89*

Author Affiliations

1 School of Medicine, Chung Shan Medical University, Taichung, Taiwan

2 Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

3 Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan

4 Department of Biotechnology, Asia University, Taichung, Taiwan

5 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan

6 School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

7 Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan

8 Institute of Medicine, Chung Shan Medical University, 110 Section 1, Chien-Kuo N. Road, South District, Taichung, Taiwan

9 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

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BMC Complementary and Alternative Medicine 2014, 14:141  doi:10.1186/1472-6882-14-141

Published: 30 April 2014

Abstract

Background

The survival rate of malignant tumors, and especially hepatocellular carcinoma (HCC), has not improved primarily because of uncontrolled metastasis. In our previous studies, we have reported that Terminalia catappa leaf extract (TCE) exerts antimetastasis effects on HCC cells. However, the molecular mechanisms of urokinase-type plasminogen activator (u-PA) in HCC metastasis have not been thoroughly investigated, and remain poorly understood.

Methods

The activities and protein levels of u-PA were determined by casein zymography and western blotting. Transcriptional levels of u-PA were detected by real-time PCR and promoter assays.

Results

We found that treatment of Huh7 cells with TCE significantly reduced the activities, protein levels and mRNA levels of u-PA. A chromatin immunoprecipitation (ChIP) assay showed that TCE inhibited the transcription protein of nuclear factors SP-1 and NF-κB. TCE also did inhibit the effects of u-PA by reducing the phosphorylation of ERK1/2 pathway.

Conclusions

These results show that u-PA expression may be a potent therapeutic target in the TCE-mediated suppression of HCC metastasis.

Keywords:
Hepatocellular carcinoma; Terminalia catappa; Migration; Invasion; u-PA