Effects of novel human cathepsin S inhibitors on cell migration in human cancer cells

摘要

Elevated cathepsin S (Cat S) level is correlated with higher migration ability in tumor cells. This study investigates the inhibitory effect of novel synthetic alpha-ketoamide compounds on cathepsin activity and cancer cell migration. The effect of several alpha-ketoamide compounds on the activity of recombinant cathepsins (Cat S, Cat L and Cat K) was examined. Two highly metastatic cancer cell lines were incubated with three Cat S-specific compounds (6n, 6w and 6r) to analyze their effect on cellular Cat S activity and cell migration. At a 100 nM concentration, compounds 6n, 6r and 6w effectively inhibited Cat S activity. Cat S activity and cell migration were significantly reduced in CL1-3 cells after treatment with either 6n or 6w at 5 mu M. Similar results were also obtained when A2058 cells were treated with 6n. These results highlight the therapeutic potential of alpha-ketoamide compounds, especially 6n and 6w, to prevent or delay cancer metastasis.