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

International Journal of Molecular Sciences

Yu-Jen Wu³  Choo-Aun Neoh¹  Chia-Yu Tsao²  Jui-Hsin Su²  Hsing-Hui Li² 

[1] Department of Research, Pingtung Christian Hospital, Pingtung 90059, Taiwan; E-Mail:;Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 94450, Taiwan; E-Mails:;Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan; E-Mail:

关键词: hepatocellular carcinoma (HCC);    Sinularia flexibilis;    sinulariolide;    matrix metalloproteinase-2/-9;    migration;    invasion;   

DOI  :  10.3390/ijms160716469

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.