Caspase-8 activation and bid cleavage contribute to MCF7 cellular execution in a caspase-3-dependent manner during staurosporine-mediated apoptosis

There are at least two distinct classes of caspases, initiators (e.g. caspa ses-8, -9, and -10) and effecters (e.g. caspase-3), Furthermore, it is beli eved that there are two distinct primary apoptotic signaling pathways, one of which is mediated by death receptors controlled by caspases-8/10, and th e other by the release of cytochrome c and activation of a caspase-9/Apaf1/ cytochrome c apoptosome. However, several recent reports have demonstrated that caspase-8, and its substrate Bid, are frequently activated in response to certain apoptotic stimuli in a death receptor-independent manner. These results suggest that significant cross talk may exist between these two di stinct signaling arms, allowing each to take advantage of elements unique t o the other. Here we provide evidence that activation of caspase-8, and sub sequent Bid cleavage, does indeed participate in cytochrome c-mediated apop tosis, at least in certain circumstances and cell types. Furthermore, the p articipation of activated caspase-3 is essential for activation of caspase- 8 and Bid processing to occur. Although caspase-8 activation is not require d for the execution of a cytochrome c-mediated death signal, we found that it greatly shortens the execution time. Thus, caspase-8 involvement in cyto chrome c-mediated cell death may help to amplify weaker death signals and e nsure that apoptosis occurs within a certain time frame.