Proposed scheme for CdA-induced apoptosis in CEM cells.

Resistance to CdA is characterized by a lack of cytochrome c release, which is preceded by an abrogation of cytosolic Ca²⁺elevations and subsequent induction of MPT. CdA treatment causes a decrease in mitochondrial Ca²⁺ buffering capacity in sensitive CEM 0 cells but not in any of the resistant cell lines. Consequently, there is no caspase-3–like or caspase-9–like activity in CdA-resistant cells. The cell-permeable Ca²⁺ chelator, BAPTA-AM (50 μM), blocks CdA-induced caspase activation and DNA fragmentation in parental cells, suggesting that mitochondria may be a target for Ca²⁺-dependent apoptotic events initiated by CdA.