当前位置： SCI文献检索 > BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS期刊下所有文献 > A novel cantharidin analog N-benzylcantharidinamide reduces the expression of MMP-9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR.

A novel cantharidin analog N-benzylcantharidinamide reduces the expression of MMP-9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR.

Abstract：

:Invasion and metastasis are major causes of malignant tumor-associated mortality. The present study aimed to investigate the molecular events underlying inhibitory effect of N-benzylcantharidinamide, a novel synthetic analog of cantharidin, on matrix metalloproteinase-9 (MMP-9)-mediated invasion in highly metastatic hepatocellular carcinoma Hep3B cells. In this investigation, among six analogs of cantharidin, only N-benzylcantharidinamide has the inhibitory action on MMP-9 expression at non-toxic dose. The MMP-9 expression and invasion of Hep3B cells were significantly suppressed by treatment of N-benzylcantharidinamide in a dose-dependent manner. On the other hand, the transcriptional activity of MMP-9 promoter and nuclear levels of NF-κB and AP-1 as the main transcriptional factors inducing MMP-9 expression were not affected by it although the level of MMP-9 mRNA was reduced by treatment of N-benzylcantharidinamide. Interestingly, the stability of MMP-9 mRNA was significantly reduced by N-benzylcantharidinamide-treatment. In addition, the cytosolic translocation of human antigen R (HuR), which results in the increase of MMP-9 mRNA stability through interaction of HuR with 3'-untranslated region of MMP-9 mRNA, was suppressed by treatment of N-benzylcantharidinamide, in a dose-dependent manner. Taken together, it was demonstrated, for the first time, that N-benzylcantharidinamide suppresses MMP-9 expression by reducing HuR-mediated MMP-9 mRNA stability for the inhibition of invasive potential in highly metastatic Hep3B cells.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Lee JY,Chung TW,Choi HJ,Lee CH,Eun JS,Han YT,Choi JY,Kim SY,Han CW,Jeong HS,Ha KT

doi

10.1016/j.bbrc.2014.04.035

subject

Has Abstract

pub_date

2014-05-02 00:00:00

pages

371-7

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(14)00666-4

journal_volume

447

pub_type

杂志文章

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