Inhibitory effect of the carnosine-gallic acid synthetic peptide on MMP-2 and MMP-9 in human fibrosarcoma HT1080 cells

• Published in: Journal of peptide science Vol. 20; no. 9; pp. 716 - 724
• Main Authors: Kim, Sung-Rae, Eom, Tae-Kil, Byun, Hee-Guk
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-09-2014; Wiley Subscription Services, Inc
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Carnosine - chemical synthesis; Carnosine - chemistry; Carnosine - pharmacology; carnosine-gallic acid peptide; Cell Line, Tumor; Cell Movement - drug effects; Fibrosarcoma - drug therapy; Fibrosarcoma - enzymology; Fibrosarcoma - pathology; Gallic Acid - chemical synthesis; Gallic Acid - chemistry; Gallic Acid - pharmacology; HT1080 cell; Humans; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase Inhibitors - chemical synthesis; Matrix Metalloproteinase Inhibitors - chemistry; matrix metalloproteinase-2 and -9; Neoplasm Invasiveness; Peptides; Peptides - chemical synthesis; Peptides - chemistry; Peptides - pharmacology; urokinase plasminogen; HT1080 cell; matrix metalloproteinase-2 and -9; carnosine-gallic acid peptide; urokinase plasminogen
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.2658

Matrix metalloproteinases (MMPs) are a family of zinc‐dependent endopeptidases that degrade extracellular matrix components and play important roles in a variety of biological and pathological processes such as malignant tumor metastasis and invasion. In this study, we constructed carnosine–gallic acid peptide (CGP) to identify a better MMP inhibitor than carnosine. The inhibitory effects of CGP on MMP‐2 and MMP‐9 were investigated in the human fibrosarcoma (HT1080) cell line. As a result, CGP significantly decreased MMP‐2 and MMP‐9 expression levels without a cytotoxic effect. Moreover, CGP may inhibit migration and invasion in HT1080 cells through the urokinase plasminogen activator (uPA)–uPA receptor signaling pathways to inhibit MMP‐2 and MMP‐9. Based on these results, it appears that CGP may play an important role in preventing and treating several MMP‐2 and MMP‐9‐mediated health problems such as metastasis. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
The carnosine–gallic acid peptide (CGP) has strongly inhibited migration and invasion in HT1080 cells through the uPA and uPAR signaling pathways to inhibit MMP‐2 and ‐9.