Processing of procaspase-8 and Bid.

Cotreatment with CGP57148 (CGP) sensitizes HL-60/Bcr-Abl and K562 cells to Ara-C–induced or doxorubicin (Dox)-induced caspase-8 and Bid processing, as well as cytosotic accumulation of cyt c and the processing of poly (ADP-ribose) polymerase (PARP). Cells were treated with 0.25 μmol/L CGP, Ara-C, or Dox alone, or with a combination of CGP plus Ara-C or CGP plus Dox for 48 hours. Following this, Western analyses of Bid, caspase-8, 116-kd PARP, and its 85-kd cleavage product and β-actin were performed on cellular proteins, or S100 fractions were used for immunoblot analysis for cyt c (see text). Expression levels are representative of 3 separate experiments.