Salinomycin inhibits hepatocellular carcinoma cell invasion and migration through JNK/JunD pathway-mediated MMP9 expression.

Abstract	The antibiotic salinomycin (Salin) was recently identified as an antitumor drug for the treatment of several types of solid tumors. However, the effects of Salin on the migratory and invasive properties of hepatocellular carcinoma (HCC) cells are unclear. The present study aimed to determine the antitumor efficacy and mechanism of Salin in HCC cells. Human HCC cells (HCCLM3) treated with Salin showed a concentration-dependent reduction in cell migration and invasion, and this was associated with reduced MMP9 expression. The MMP9 promoter and enhancer in a luciferase reporter assay revealed that Salin can regulate MMP9 expression through an activator protein (AP-1) site within the MMP9 enhancer. JunD, one of the AP-1 components, was significantly decreased by Salin in a concentration- and time-dependent manner. Salin was able to induce c-Jun NH2-kinase (JNK) phosphorylation and to block both JunD and MMP9 expression. Our results showed that JNK phosphorylation and JunD may be involved in the Salin-regulated MMP9 signaling pathway in HCCLM3 cells and may mediate HCC cell biological characteristics. Our studies provide new insight into the antitumor effects of Salin.
Authors	Ling Xu, Ting Wang, Wen-Ying Meng, Jue Wei, Jia-Li Ma, Min Shi, Yu-Gang Wang
Journal	Oncology reports (Oncol Rep) Vol. 33 Issue 3 Pg. 1057-63 (Mar 2015) ISSN: 1791-2431 [Electronic] Greece
PMID	25522777 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents JunD protein, human Proto-Oncogene Proteins c-jun Pyrans salinomycin MMP9 protein, human Matrix Metalloproteinase 9
Topics	Antineoplastic Agents (pharmacology) Blotting, Western Carcinoma, Hepatocellular (metabolism, pathology) Cell Line, Tumor Cell Movement (drug effects) Enzyme-Linked Immunosorbent Assay Humans Liver Neoplasms (metabolism, pathology) MAP Kinase Signaling System (drug effects) Matrix Metalloproteinase 9 (biosynthesis) Proto-Oncogene Proteins c-jun (metabolism) Pyrans (pharmacology)

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