1-(5-Bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] Inhibits MMP-9 Expression by Regulating NF-κB and MAPKs Signaling Pathways in HT1080 Human Fibrosarcoma Cells.

Fang Gong,Zhong-Ji Qian,Chengyong Li,Bomi Ryu,Pengzhi Hong,Jiachao Lin,Chunxia Zhou,Yuanyuan Zhang

doi:10.1155/2018/5639486

Abstract

Hippocampus is a traditional medicine in China, which can be used for treating tumors, aging, fatigue, thrombosis, inflammation, hypertension, prostatic hyperplasia, and other diseases. 1-(5-Bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] from seahorse (Hippocampus kuda Bleeler) has been shown to suppress proinflammatory responses. In the present study, SE1 potently inhibited gelatin digestion by MMP-9 induced by phorbol 12-myristate 13-acetate (PMA) and migration of human fibrosarcoma HT1080 cells in dose-dependent manner. Moreover, western blot analysis and immunofluorescence analysis have been studied on MAPKs (ERK1/2, p38 kinase and JNK) and NF-κB (p65 and IκB), which refer to the clear molecular mechanism. The results indicated that SE1 significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPK: p38 kinase and JNK) and NF-κB. Finally, molecular docking result showed SE1 interacts with TYR245 and HIS226 of MMP-9 by hydrogen bond and Pi-Pi bond to suppress MMP-9 activity. This data suggested that the SE1 may possess therapeutic and preventive potential for the treatment of MMP-9 related disorders.

Highlights

Tumor is the abnormal growth of tissue and the formation of mass [1]
Previous studies indicated that matrix metalloproteinases (MMPs) have the ability to degrade extracellular matrix (ECM) and their overexpressions are to blame for tumor progression, invasion, metastasis, and angiogenesis [4,5,6]
It has been well documented that both mitogenactivated protein kinases (MAPKs) and nuclear factor kappa (NF-κB) signal pathways are related to tumor metastasis because they can control tumor cell migration and regulate MMPs expression [12, 13]

Summary

Introduction

The rapid proliferation and metastasis of tumor cells are a chief culprit of death of patients. Malignant tumor cells can invade into surrounding extracellular matrix (ECM) and degrade ECM with proteolytic enzymes to promote metastatic spread, which affect the body’s normal function [2, 3]. Previous studies indicated that matrix metalloproteinases (MMPs) have the ability to degrade ECM and their overexpressions are to blame for tumor progression, invasion, metastasis, and angiogenesis [4,5,6]. Accumulating literatures have confirmed that MMP-2 and MMP-9 function as dominating enzymes taking part in degradation of type IV collagen which is a key component of ECM [7]. It has been well documented that both mitogenactivated protein kinases (MAPKs) and nuclear factor kappa (NF-κB) signal pathways are related to tumor metastasis because they can control tumor cell migration and regulate MMPs expression [12, 13]

Methods

Results

Discussion

Conclusion