11-epi-Sinulariolide Acetate Reduces Cell Migration and Invasion of Human Hepatocellular Carcinoma by Reducing the Activation of ERK1/2, p38MAPK and FAK/PI3K/AKT/mTOR Signaling Pathways

Marine Drugs

Jen-Jie Lin¹  Jui-Hsin Su²  Chi-Chu Tsai³  Yi-Jen Chen⁴  Ming-Hui Liao¹ 

[1] Graduate Institute of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91202, Taiwan; E-Mail:;National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan; E-Mail:;Kaohsiung District Agricultural Improvement Station, Pingtung 900, Taiwan; E-Mail:;Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung 80761, Taiwan; E-Mail:

关键词: 11-epi-sinulariolide acetate;    hepatocellular carcinoma;    migration;    invasion;    matrix metalloproteinase;    ERK1/2;    p38MAPK;   

DOI  :  10.3390/md12094783

来源: mdpi

【 摘 要 】

Cancer metastasis is one of the major causes of death in cancer. An active compound, 11-epi-sinulariolide acetate (11-epi-SA), isolated from the cultured soft coral Sinularia flexibilis has been examined for potential anti-cell migration and invasion effects on hepatocellular carcinoma cells (HCC). However, the molecular mechanism of anti-migration and invasion by 11-epi-SA on HCC, along with their corresponding effects, remain poorly understood. In this study, we investigated anti-migration and invasion effects and the underlying mechanism of 11-epi-SA in HA22T cells, and discovered by trans-well migration and invasion assays that 11-epi-SA provided a concentration-dependent inhibitory effect on the migration of human HCC HA22T cells. After treatment with 11-epi-SA for 24 h, there were suppressed protein levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (uPA) in HA22T cells. Meanwhile, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase-2 (TIMP-2) were increased in a concentration-dependent manner. Further investigation revealed that 11-epi-SA suppressed the phosphorylation of ERK1/2 and p38MAPK. The 11-epi-SA also suppressed the expression of the phosphorylation of FAK/PI3K/AKT/mTOR pathways.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.