Inhibition of tumorigenesis in mouse skin by leupeptin, a protease inhibitor from Actinomycetes.

Abstract

Leupeptin, with the structure N -acetyl( N -propionyl)-l-leucyl-l-leucyl-dl-argininal, was isolated from Actinomycetes and is a potent and specific inhibitor of proteases. In this work, leupeptin was found to inhibit tumorigenesis in mouse skin induced by a single, noncarcinogenic dose of 7,12-dimethylbenz(a)anthracene followed by repeated application of croton oil. Tumors that had already been induced were scarcely affected by leupeptin. The activity of p -toluene-sulfonyl-l-arginine methyl ester esterase in mouse skin was markedly increased by treatment with croton oil and was inhibited by leupeptin both in vitro and in vivo . The effect of leupeptin in repressing tumorigenesis seems to be due to its inhibition of p -toluene-sulfonyl-l-arginine methyl ester esterase in the skin and not to a direct effect on tumors.