Salidroside, 8(E)-Nuezhenide, and Ligustroside from Ligustrum japonicum Fructus Inhibit Expressions of MMP-2 and -9 in HT 1080 Fibrosarcoma.

Hojun Kim,Youngwan Seo,Chang-Suk Kong

doi:10.3390/ijms23052660

Abstract

A phenyl ethanoid, salidroside (SAL), and two secoiridoids, 8(E)-nuezhenide (NZD) and ligustroside (LIG), were isolated from fruits of Ligustrum japonicum, used as traditional folk medicine, and their chemical structures were elucidated by the comparison of spectral data with published literature. Matrix metalloproteinases (MMPs) are major enzymes that play crucial roles in the metastasis and invasive behavior of tumors. In particular, MMP-2 and MMP-9, regulated by the MAPK signaling pathways, including p38, ERK and JNK, are known to play a key role in the degradation of the basement membrane. In the present study, the effects of SAL, NZD and LIG on the expression of MMP-2 and -9 were examined in phorbol 12-myristate 13-acetate (PMA)-induced HT 1080 cells. All the compounds significantly lowered the amount of MMP-2 and MMP-9 released, as determined by gelatin zymography and ELISA. In addition, the mRNA and protein expression levels of MMP-2 and MMP-9 were significantly suppressed, as measured by RT-PCR and Western blotting. According to the Western blotting assay, SAL and LIG effectively reduced the expression of MMP-2 in a dose-dependent manner. NZD lowered the expression of MMP-9 in a similar way. The phosphorylation of p38, ERK and JNK was also significantly suppressed by these compounds. These findings suggest that all the compounds regulate the release and expression of MMP-2 and MMP-9 via MAPK signaling pathways.

Highlights

The phosphorylation of p38, ERK and JNK was significantly suppressed by these compounds. These findings suggest that all the compounds regulate the release and expression of Matrix metalloproteinases (MMPs)-2 and MMP-9 via mitogen-activated protein kinase (MAPK) signaling pathways
Because of the key role that MMPs play in tumorigenesis and metastasis, modulation of MMP expression could be a strategic target for the development of cancer-fighting and therapeutic methods
We report the isolation of salidroside their effects on the activation and expression of MMP-2 and MMP-9 in the HT1080 human (SAL), 8(E)-nuezhenide fibrosarcoma cell line. (NZD) and ligustroside (LIG), and their effects on the activation and expression of MMP-2 and MMP-9 in the HT1080 human fibrosarcoma cell line

Summary

Introduction

The extracellular matrix functions as a structural support for the cells, and plays a major role in cancer metastasis, tissue formation, intercellular communication and gene expression. Matrix metalloproteinases (MMPs) act on the degradation and remodeling of the extracellular matrix, and are involved in the release of various signaling proteins [4,5]. Among the MMPs in the human body, MMP-2 and MMP-9, which are gelatinases, are known to digest type IV collagen, a major component of the extracellular matrix, and to induce cancer cell invasion and metastasis by participating in both basement membrane degradation and the formation of new blood vessels [6–8]. Because of the key role that MMPs play in tumorigenesis and metastasis, modulation of MMP expression could be a strategic target for the development of cancer-fighting and therapeutic methods

Methods

Results

Conclusion