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Int. J. Mol. Sci. 2015, 16(7), 16469-16482; doi:10.3390/ijms160716469

Sinulariolide Suppresses Human Hepatocellular Carcinoma Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 through MAPKs and PI3K/Akt Signaling Pathways

1
Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan
2
Department of Research, Pingtung Christian Hospital, Pingtung 90059, Taiwan
3
Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 94450, Taiwan
4
Industry Academia Collaboration Center, National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 2 June 2015 / Revised: 9 July 2015 / Accepted: 13 July 2015 / Published: 20 July 2015
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)
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Abstract

Sinulariolide is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigate the migration and invasion effects of sinulariolide in hepatocellular carcinoma cell HA22T. Sinulariolide inhibited the migration and invasion effects of hepatocellular carcinoma cells in a concentration-dependent manner. The results of zymography assay showed that sinulariolide suppressed the activities of matrix metalloproteinase (MMP)-2 and MMP-9. Moreover, protein levels of MMP-2, MMP-9, and urokinase-type plasminogen activator (uPA) were reduced by sinulariolide in a concentration-dependent manner. Sinulariolide also exerted an inhibitory effect on phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), phosphatidylinositol 3-kinase (PI3K), Akt, Focal adhesion kinase (FAK), growth factor receptor-bound protein 2 (GRB2). Taken together, these results demonstrated that sinulariolide could inhibit hepatocellular carcinoma cell migration and invasion and alter HA22T cell metastasis by reduction of MMP-2, MMP-9, and uPA expression through the suppression of MAPKs, PI3K/Akt, and the FAK/GRB2 signaling pathway. These findings suggest that sinulariolide merits further evaluation as a chemotherapeutic agent for human hepatocellular carcinoma. View Full-Text
Keywords: hepatocellular carcinoma (HCC); Sinularia flexibilis; sinulariolide; matrix metalloproteinase-2/-9; migration; invasion hepatocellular carcinoma (HCC); Sinularia flexibilis; sinulariolide; matrix metalloproteinase-2/-9; migration; invasion
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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. (CC BY 4.0).

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MDPI and ACS Style

Wu, Y.-J.; Neoh, C.-A.; Tsao, C.-Y.; Su, J.-H.; Li, H.-H. Sinulariolide Suppresses Human Hepatocellular Carcinoma Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 through MAPKs and PI3K/Akt Signaling Pathways. Int. J. Mol. Sci. 2015, 16, 16469-16482.

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