GDC-0152-induced autophagy promotes apoptosis in HL-60 cells.

GDC-0152 is a new type of chemical compound which can downregulate inhibitor of apoptosis protein. We previously reported that GDC-0152 induced apoptosis in HL-60 cells in a caspase-dependent manner. In this study, we have focused on GDC-0152-induced autophagy and the relationship between apoptosis and autophagy. We found that GDC-0152 can evoke autophagy flux as confirmed by the upregulation of LC3 and downregulation of p62. The conversion of LC3I to LC3II verified the existence of autophagy flux further. GDC-0152 induced autophagy through downregulating B cell lymphoma 2 and Bcl-2-interacting myosin-like coiled-coil protein, and upregulating WD-repeat domain phosphoinositide-interacting protein 1. Pretreating HL-60 cells with autophagy inhibitor Bafolimycin A1 reduced GDC-0152-induced apoptosis. However, pretreatment with caspase inhibitor Z-VAD-FMK had no effect on autophagy. Reactive oxygen species were released in GDC-0152-treated HL-60 cells but did not take part in the regulation of autophagy and apoptosis. In conclusion, our findings suggest that GDC-0152-induced autophagy can trigger apoptosis in HL-60 cells.