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Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 595292, 11 pages
http://dx.doi.org/10.1155/2012/595292
Research Article

Terminalia catappa Exerts Antimetastatic Effects on Hepatocellular Carcinoma through Transcriptional Inhibition of Matrix Metalloproteinase-9 by Modulating NF-κB and AP-1 Activity

1School of Medicine, Chung Shan Medical University, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan
2Department of Emergency Medicine, Chung Shan Medical University, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan
3Department of Emergency Medicine, Chung Shan Medical University Hospital, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan
4School of Medical Laboratory and Biotechnology, Chung Shan Medical University, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan
5Institute of Biochemistry and Biotechnology, Chung Shan Medical University, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan
6Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
7Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
8School of Pharmacy, Taipei Medical University, Taipei, Taiwan
9Institute of Medicine, Chung Shan Medical University, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan
10Department of Medical Research, Chung Shan Medical University Hospital, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan

Received 4 July 2012; Accepted 16 August 2012

Academic Editor: Seung-Heon Hong

Copyright © 2012 Chao-Bin Yeh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. Previous studies have identified that Terminalia catappa leaf extracts (TCE) exert hepatoprotective, antioxidative, antiinflammatory, anticancer, and antimetastatic activities. However, the effects of TCE on HCC and the underlying molecular mechanisms of its activities have yet to be fully elucidated. The present study's findings demonstrate that TCE concentration dependently inhibits human HCC migration/invasion. Zymographic and western blot analyses revealed that TCE inhibited the activities and expression of matrix metalloproteinase-9 (MMP-9). Assessment of mRNA levels, using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR, and promoter assays confirmed the inhibitory effects of TCE on MMP-9 expression in HCC cells. The inhibitory effects of TCE on MMP-9 proceeded by upregulating tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as suppressing nuclear translocation and DNA binding activity of nuclear factor-kappa B (NF-κB) and activating protein-1 (AP-1) on the MMP-9 promoter in Huh7 cells. In conclusion, TCE inhibits MMP-9 expression and HCC cell metastasis and, thus, has potential use as a chemopreventive agent. Its inhibitory effects are associated with downregulation of the binding activities of the transcription factors NF-κB and AP-1.