Synthesis of procaspases-3 and-7 during apoptosis in prostate cancer cells

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 co mponents of the death pathway. TSU-Prl prostate cancer cells treated with o kadaic acid demonstrated activation of caspase-3, PARP cleavage, and nuclea r fragmentation by 24 h and apoptosis by 72 h, Levels of procaspase-3 and p rocaspase-7, the precursor molecules of two effector caspases, were not dep leted during apoptosis, Levels of procaspase-3 and -7 mRNA increased steadi ly in TSU-Prl cells up to 72 h after exposure to okadaic acid. Nuclear run- off experiments showed that the increase in mRNA was not due to transcripti onal activation of caspase-3 and -7 mRNA, Antisense caspase-3 and caspase-7 oligodeoxynucleotides caused a depletion of procaspases-3 and -7 and a del ay in apoptosis of TSU-Prl cells. Caspase antisense oligodeoxynucleotides i nhibited apoptosis to a similar extent as peptide inhibitors of cysteine pr oteases. Synthesis of procaspases-3 and -7 was necessary to sustain program med cell death in TSU-Prl prostate cancer cells.