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.