Stellettin B Suppresses Human Hepatocellular Cacinoma Cell Migration and Invasion through MAPK and FAK/PI3K/AKT/mTOR Signaling Pathways
Wu Yu-Jen 1, Neoh Choo-Aun 2, Chang Han-Tsung 3, Su Jui-Hsin 4, Liu Chih-I 5
1 Department of Biological Technology, Meiho Universtiy, Pingtung, Taiwan
2 Department of Research, Pingtung Christian Hospital, Pingtung, Taiwan
3 Graduate Institute of Applied Healthy and Biotechnology, Meiho University, Pingtung, Taiwan
4 National Museum of Marine Biology and Aquarium, Pingtung, Taiwan
5 Department of Nursing, Meiho University, Pingtung, Taiwan
Stellettin B, isolated by wild-type sponge Stelletta sp. from the ocean, exhibited potent antiprolifertive activities on various tumor cells. In this study, we use demonstrated the stellettin B inhibited the migration and invasion of the hepatocellular carcinoma cell HA22T/VGH. We found that the stellettin B inhibited the invasion and migration of hepatocellular carcinoma cells in a dose-dependent manner. The results of zymography assay showed that stellettin B suppressed the activities of matrix metalloproteinase MMP-9 and MMP-2. Moreover, protein levels of MMP-9, MMP-2, and urokinase-type plasminogen activator (uPA) were reduced by stellettinB in a dose-dependent manner. Stellettin B also exerted an inhibitory effect on phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), phosphatidylinositol 3-kinase (PI3K) and Akt. Taken together, these results demonstrated that stellettin B could inhibit hepatocellular carcinoma cell migration and invasion and alter HA22T/VGH cell metastasis by reduction of uPA , MMP-2 and MMP-9 expression through the suppression of MAPKs and FAK/PI3K/AKT/mTOR signaling pathway. These findings suggest that stellettin B merits further evaluation as a chemotherapeutic agent for human hepatocellular carcinoma.
