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

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2014 Sep 16

PMID 25222667

Citations 31

Authors

Jen-Jie Lin

Jui-Hsin Su

Chi-Chu Tsai

Yi-Jen Chen

Ming-Hui Liao

Yu-Jen Wu

Affiliations

Soon will be listed here.

Abstract

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.

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