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Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 732578, 10 pages
http://dx.doi.org/10.1155/2012/732578
Research Article

Caffeic Acid Phenethyl Ester Inhibits Oral Cancer Cell Metastasis by Regulating Matrix Metalloproteinase-2 and the Mitogen-Activated Protein Kinase Pathway

1School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan
2Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
3Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
4School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan
5Department of Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan
6Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
7Institute of Oral Sciences, Chung Shan Medical University, Taichung 40201, Taiwan

Received 30 September 2012; Revised 10 November 2012; Accepted 19 November 2012

Academic Editor: Shrikant Anant

Copyright © 2012 Chih-Yu Peng 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

Caffeic acid phenethyl ester (CAPE), an active component extracted from honeybee hives, exhibits anti-inflammatory and anticancer activities. However, the molecular mechanism by which CAPE affects oral cancer cell metastasis has yet to be elucidated. In this study, we investigated the potential mechanisms underlying the effects of CAPE on the invasive ability of SCC-9 oral cancer cells. Results showed that CAPE attenuated SCC-9 cell migration and invasion at noncytotoxic concentrations (0 μM to 40 μM). Western blot and gelatin zymography analysis findings further indicated that CAPE downregulated matrix metalloproteinase-2 (MMP-2) protein expression and inhibited its enzymatic activity. CAPE exerted its inhibitory effects on MMP-2 expression and activity by upregulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and potently decreased migration by reducing focal adhesion kinase (FAK) phosphorylation and the activation of its downstream signaling molecules p38/MAPK and JNK. These data indicate that CAPE could potentially be used as a chemoagent to prevent oral cancer metastasis.