Induction of cell death in neuroblastoma by inhibition of cathepsins B and L.
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.
Colella
Rita
R
Department of Anatomical Sciences & Neurobiology, University of Louisville School of Medicine, Louisville, KY 40292, United States.
Lu
Guizhen
G
Glazewski
Lisa
L
Korant
Bruce
B
Matlapudi
Anjan
A
England
Matthew R
MR
Craft
Colin
C
Frantz
Christopher N
CN
Mason
Robert W
RW
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*
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