Z-Phe-Gly-NHO-Bz, an inhibitor of cysteine cathepsins, induces apoptosis in human cancer cells

An increasing number of studies indicate that cysteine cathepsins contribut e to cancer progression, invasion, and metastasis. Here we provide experime ntal evidence that the cathepsin inhibitor Z-Phe-Gly-NHO-Bz induces rapid a poptotic death in human cancer cell lines. Notably, the Z-Phe-Gly-NHO-Bz-in duced apoptosis exhibited independence of p53, caspases. and mitogen-activa ted protein (MAP) kinases. Taken together, our results prompt the hypothesi s that cysteine cathepsin(s) is a universal survival factor for cancer cell s, and its inhibition leads to cancer cell apoptosis. The exquisite sensiti vity of human cancer cells to CATI-1 indicates that this compound and its d erivatives may provide the basis for new treatment programs against abroad spectrum of malignancies.