title: Synthesis of procaspases-3 and -7 during apoptosis in prostate cancer cells.
abstract: Cells differ in the time required to execute cell death after receipt of a death signal. One reason may be the requirement for de novo synthesis of components of the death pathway. TSU-Pr1 prostate cancer cells treated with okadaic acid demonstrated activation of caspase-3, PARP cleavage, and nuclear fragmentation by 24 h and apoptosis by 72 h. Levels of procaspase-3 and procaspase-7, the precursor molecules of two effector caspases, were not depleted during apoptosis. Levels of procaspase-3 and -7 mRNA increased steadily in TSU-Pr1 cells up to 72 h after exposure to okadaic acid. Nuclear run-off experiments showed that the increase in mRNA was not due to transcriptional activation of caspase-3 and -7 mRNA. Antisense caspase-3 and caspase-7 oligodeoxynucleotides caused a depletion of procaspases-3 and -7 and a delay in apoptosis of TSU-Pr1 cells. Caspase antisense oligodeoxynucleotides inhibited apoptosis to a similar extent as peptide inhibitors of cysteine proteases. Synthesis of procaspases-3 and -7 was necessary to sustain programmed cell death in TSU-Pr1 prostate cancer cells.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Lombardi Cancer Center, Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, District of Columbia 20007-2197, USA.
authors.forename: C
authors.initials: C
authors.lastname: Bowen
authors.forename: H J
authors.initials: HJ
authors.lastname: Voeller
authors.forename: K
authors.initials: K
authors.lastname: Kikly
authors.forename: E P
authors.initials: EP
authors.lastname: Gelmann
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000096:biosynthesis*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D019319:Okadaic Acid / Q000494:pharmacology; D020319:Oligodeoxyribonucleotides, Antisense; D011471:Prostatic Neoplasms; D014407:Tumor Cells, Cultured
chemical_list: D004792:Enzyme Precursors; D020319:Oligodeoxyribonucleotides, Antisense; D019319:Okadaic Acid; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases