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

Journal of enzyme inhibition and medicinal chemistry (2013-10-03)
Ju-Ying Tsai, Mon-Juan Lee, Margaret Dah-Tsyr Chang, Hsin-Chieh Wang, Chun-Cheng Lin, Haimei Huang
ABSTRACT

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

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
E-64, protease inhibitor
Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, essentially IgG-free, low endotoxin, BioReagent, suitable for cell culture
Sigma-Aldrich
7-Amino-4-methylcoumarin, 99%
Sigma-Aldrich
7-Amino-4-methylcoumarin, Chromophore for substrates
Sigma-Aldrich
β-D-Allose, rare aldohexose sugar

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