title: Z-Phe-Gly-NHO-Bz, an inhibitor of cysteine cathepsins, induces apoptosis in human cancer cells.
abstract: An increasing number of studies indicate that cysteine cathepsins contribute to cancer progression, invasion, and metastasis. Here we provide experimental evidence that the cathepsin inhibitor Z-Phe-Gly-NHO-Bz induces rapid apoptotic death in human cancer cell lines. Notably, the Z-Phe-Gly-NHO-Bz-induced apoptosis exhibited independence of p53, caspases, and mitogen-activated protein (MAP) kinases. Taken together, our results prompt the hypothesis that cysteine cathepsin(s) is a universal survival factor for cancer cells, and its inhibition leads to cancer cell apoptosis. The exquisite sensitivity of human cancer cells to CATI-1 indicates that this compound and its derivatives may provide the basis for new treatment programs against a broad spectrum of malignancies.
authors.affiliation: Department of Immunology, Parker Hughes Cancer Center, Parker Hughes Institute, Roseville, Minnesota 55113, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Zhu
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D016159:Tumor Suppressor Protein p53; C412454:phenylalanyl-glycyl-NHO-Bz; D020928:Mitogen-Activated Protein Kinases; D002403:Cathepsins; D020169:Caspases