Lactacystin, a specific inhibitor of the proteasome, induces apoptosis in human monoblast U937 cells.
Lactacystin, originally isolated from a microbe as an inducer of neuritogenesis, targets the catalytic beta-subunit of the proteasome, and arrests the cell cycle. Here we report for the first time that lactacystin induces apoptotic cell death in human monoblastic U937 cells. When U937 cells were cultured with lactacystin, their nuclei were shrunken, a morphological change typical of apoptosis, and cell viability was decreased. Electrophoretic analysis revealed that chromosomal DNAs from lactacystin-treated cells were cleaved in an internucleosomal ladder-like pattern, indicating that cell death occurs through an apoptotic process, which was also confirmed by DNA fragmentation analysis using flow cytometry. These findings suggest that inhibition of the proteasome during proliferation results in apoptotic cell death, and that the proteasome is a key enzyme in the course of the cell cycle that destines the cell to proliferate, differentiate or die.
Imajoh-Ohmi
S
S
Institute of Medical Science, University of Tokyo, Japan.
Kawaguchi
T
T
Sugiyama
S
S
Tanaka
K
K
Omura
S
S
Kikuchi
H
H
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004249:DNA Damage; D006801:Humans; D009000:Monocytes / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; C067713:lactacystin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine