AKT inhibition by API-2 treatment or DN-AKT transfection induces chemosensitivity to docetaxel via a caspase-3–dependent pathway. A, DU145-DR and PC3-DR tumor cells, pretreated with API-2 or DN-AKT transfection (including DMSO or PCDNA3 controls), were treated with zVAD.fmk, a general caspase inhibitor, and zVAD.amc, a caspase-1–specific inhibitor. These cells were then exposed to docetaxel for 48 h before analysis of active caspase-3. High levels of active caspase-3 were detected in API-treated and DN-AKT–expressing tumor cells. This activity was inhibited by zVAD.fmk but not by zVAD.amc. B, visual assessment of cell survival by methylene blue staining of the same cells showed few cells surviving in DU145DR and PC3-DR tumor cells treated with API-2 or transfected with DN-AKT, whereas the control DMSO–treated and PCDNA3-expressing cells showed a robust growth.