title: Induction of cell death in neuroblastoma by inhibition of cathepsins B and L.
abstract: A specific irreversible inhibitor of both cathepsins B and L, Fmoc-Tyr-Ala-CHN(2) (FYAD) induced apoptosis of neuroblastoma cells but not other tumor cells. Cysteine protease inhibitors that were not efficient inhibitors of both proteases did not cause death of any cell line tested. Apoptosis was preceded by accumulation of large electron dense vesicles and multivesicular bodies in the cytoplasm. Exposure of cells to the cathepsin D inhibitor, pepstatin, failed to rescue cells from FYAD-induced death. These results indicate that inhibition of cathepsins B and L may provide a unique mechanism for selectively inducing death of neuroblastoma with limited toxicity to normal cells and tissues.
authors.affiliation: Department of Anatomical Sciences & Neurobiology, University of Louisville School of Medicine, Louisville, KY 40292, United States.
authors.forename: Rita
authors.initials: R
authors.lastname: Colella
authors.forename: Guizhen
authors.initials: G
authors.lastname: Lu
authors.forename: Lisa
authors.initials: L
authors.lastname: Glazewski
authors.forename: Bruce
authors.initials: B
authors.lastname: Korant
authors.forename: Anjan
authors.initials: A
authors.lastname: Matlapudi
authors.forename: Matthew R
authors.initials: MR
authors.lastname: England
authors.forename: Colin
authors.initials: C
authors.lastname: Craft
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Frantz
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mason
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000235:genetics; D002402:Cathepsin D / Q000037:antagonists & inhibitors; D056668:Cathepsin L / Q000037:antagonists & inhibitors* / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005449:Fluorenes / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D015853:Cysteine Proteinase Inhibitors; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D011480:Protease Inhibitors; D002401:Cathepsin B; D056668:Cathepsin L; D002402:Cathepsin D