Actinonin induces apoptosis in U937 leukemia cells.
We have previously shown that actinonin causes inhibition of cellular proliferation in U937 leukemia cells. In this report we demonstrate that the inhibition of cell growth by actinonin occurs through the induction of apoptosis. Signs of apoptosis at high actinonin concentration included DNA fragmentation, exposure of phosphatidylserine and condensation of cell nuclei. Apoptosis caused by actinonin was inhibited by Z-VAD-FMK, a broad specificity inhibitor of caspases, implicating the caspase pathway of apoptosis. Further, apoptosis was associated with a large increase in intracellular caspase-3 and -7 activities.
Grujic
Mirjana
M
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia. mirjana.grujic@bmc.uu.se
Zavasnik-Bergant
Tina
T
Pejler
Gunnar
G
Renko
Metka
M
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053179:Caspase 7; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004249:DNA Damage; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007938:Leukemia / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D000900:Anti-Bacterial Agents; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D006877:Hydroxamic Acids; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases; C010531:actinonin