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.
Nishimura
C
C
Institute of Applied Microbiology, University of Tokyo.
Nishimura
T
T
Tanaka
N
N
Yamaguchi
H
H
Suzuki
H
H
D000818:Animals; D001761:Bleomycin / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003546:Cysteine Endopeptidases; D004357:Drug Synergism; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D017663:Peplomycin; D011480:Protease Inhibitors / Q000494:pharmacology*
D011480:Protease Inhibitors; D001761:Bleomycin; D017663:Peplomycin; D006026:Glycoside Hydrolases; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase; D007930:Leucine; C024974:E 64