Abstract
The current study investigated the ability of two secoiridoids, GL-3 (1) and oleonuezhenide (2), isolated from the fruits of Ligustrum japonicum to inhibit MMP-2 and -9 activity in phorbol 12-myristate 13-acetate (PMA)-induced HT-1080 human fibrosarcoma cells. Both compounds 1 and 2 were able to exert lowered gelatin digestion activity for MMP-2 and -9 tested by gelatin zymography via suppressing the release of MMPs to culture medium according to ELISA results. Treatment with compounds was also able to suppress the expression of both mRNA and protein levels of MMP-2 and -9. Action mechanism behind the MMP inhibitory effect of the compounds was suggested to be via MAPK pathway indicated by decreased levels of phosphorylated p38, ERK and JNK proteins evaluated employing immunoblotting. Compound 1 was shown to be slightly more active to inhibit MMP-2 and -9, however, compound 2 showed more regular dose-dependency during inhibition. In conclusion, this study suggested that GL-3 and oleonuezhenide were notable natural origin potent MMP inhibitors and could serve as lead compounds for development of anti-invasive MMP inhibitors against tumor metastasis.
Highlights
Matrix metalloproteinases (MMPs) are a family of Zn2+ dependent endopeptidases with more than 20 members which take roles in several diseases and complications such as chronic inflammation, periodontitis, chronic obstructive pulmonary disease, arteriosclerosis and arthritis [1,2,3]
MMPs are known to be crucial in the progression, metastasis and invasion of the tumor cells owing to their ability to degrade and regenerate extracellular matrix [4,5]
JNK proteins of mitogen-activated protein kinase (MAPK) pathway. (a) Cells were treated with indicated concentrations of compounds 1
Summary
Matrix metalloproteinases (MMPs) are a family of Zn2+ dependent endopeptidases with more than 20 members which take roles in several diseases and complications such as chronic inflammation, periodontitis, chronic obstructive pulmonary disease, arteriosclerosis and arthritis [1,2,3]. MMPs are known to be crucial in the progression, metastasis and invasion of the tumor cells owing to their ability to degrade and regenerate extracellular matrix [4,5]. The secondary tumor growth where metastatic cancer cells from malignant tumors travel through the body via lymphatic system is closely-linked with the actions of several MMPs on the extracellular matrix of the target tissue for invasion [8,9]. It is mainly observed through MMP-mediated degradation of basement membrane proteins.
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