Inhibition of intracellular bleomycin hydrolase activity by E-64 leads to the potentiation of the cytotoxicity of peplomycin against Chinese hamster lung cells.

N-(N-(L-3-trans-carboxyoxiran-2-carbonyl)-L-leucyl)-agmatine (E-64), a thiol protease inhibitor, potentiated the cytotoxicity of peplomycin against the Chinese hamster lung (V79) cell. After the treatment of the cells with E-64 (50 micrograms/ml) for 12 h, bleomycin hydrolase activity of the cells was almost completely inhibited. V79 cells treated with [3H]peplomycin for 24 h in the presence of E-64 (50 micrograms/ml) accumulated twice as much [3H]peplomycin and five times less [3H]desamidopeplomycin compared with V79 cells treated in the absence of E-64. These results suggest that E-64 increases the sensitivity of V79 cells to peplomycin probably by inhibiting the intracellular bleomycin hydrolase activity.