Inhibition of caspase activity induces a switch from apoptosis to necrosis.

The role of caspases in B lymphocyte cell death was investigated by using two broad spectrum inhibitors of the caspase family, Z-Asp-cmk and Z-VAD-fmk. They totally prevented spontaneous and drug-induced apoptosis and inhibited the CPP32/caspase-3-like activity exhibited by apoptotic cells. However, the suppression of apoptosis was not associated with a long-term increase of cell survival, but conversely, with a switch from apoptotic death to the necrotic form. These results strongly suggest that apoptosis and necrosis share common initiation pathways, the final issue being determined by the presence of an active caspase.