Cathepsin inhibition induces apoptotic death in human leukemia and lymphoma cells.
We examined the effects of cathepsin inhibitor 1 (CATI-1), a selective inhibitor of cysteine cathepsins, on human leukemia and lymphoma cells. CATI-1 induced apoptosis in all 12 cell lines tested. Apoptosis of CATI-1-treated leukemia/lymphoma cells was caspase-independent, p53-independent, BAX-independent as well as MAP kinase-independent. Our findings provide unprecedented experimental evidence that cathepsins play a pivotal role for the survival of human leukemia/lymphoma cells. Therefore, cathepsin inhibitors may provide the basis for new treatment programs against leukemia and lymphoma.
Zhu
D M
DM
Parker Hughes Cancer Center; Parker Hughes Institute, 2665 Long Lake Road, Roseville, MN 55113, USA.
Uckun
F M
FM
D017209:Apoptosis / Q000187:drug effects*; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007938:Leukemia / Q000473:pathology*; D008223:Lymphoma / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004151:Dipeptides; D011480:Protease Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C412454:phenylalanyl-glycyl-NHO-Bz; D020928:Mitogen-Activated Protein Kinases; D002403:Cathepsins