Inhibitory effect of a traditional Chinese formulation, Hyul-Tong-Ryung, on PMA-induced MMP-9 expression in MCF-7 human breast carcinoma cells

Abstract

Matrix metalloproteinase-9 (MMP-9) is known to play a major role in the invasion and metastasis of cancer cells. Thus an inhibitory effect on MMP-9 is important to create a therapeutic experimental model of tumor metastasis. In recent years, traditional Chinese herbal remedies have increasingly attracted considerable attention as a new source of anticancer agent. In this study, we investigated the potential inhibitory effects of a methanolic extract of 'Hyul-Tong-Ryung' (HTR), a traditional Chinese formulation, on MMP-9 activity and expression, and the cellular invasion in the phorbol 12-myristate 13-acetate (PMA)-induced MCF-7 human breast carcinoma cells. The results of a gelatin zymography analysis showed that the methanolic extract of HTR dramatically inhibited MMP-9 activity in PMA-induced MCF-7 cells. In addition, a Matrigel invasion assay showed that HTR strongly and dose-dependently inhibited PMA-induced invasion of MCF-7 cells as compared to the control, which was not treated with PMA. Moreover, treatment of MCF-7 cells with HTR significantly decreased the levels of PMA-induced expression and translation of MMP-9 mRNA in a concentration-dependent manner. As evidenced by MMP-9 promoter assays, HTR also remarkably inhibited the transcriptional activity of the MMP-9 gene in PMA-induced MCF-7 cells. These results suggest that the methanolic extract of HTR could be used as a potential anti-metastatic agent to suppress PMA-induced cancer cell invasion through the inhibition of MMP-9 gene expression level.