Fig. 8

A schematic diagram demonstrating ONC212 induced apoptosis signalling. ONC212 induces caspase-3 activation independently of cytochrome c release and caspase-8 activation, two key events in the intrinsic and extrinsic apoptosis signaling pathways respectively. This atypical caspase-3 activation is negatively regulated by Bcl-2 and Bcl-xL in the cell. Inhibition of these proteins with Navitoclax augments caspase-3 activity, dramatically sensitizing cells to ONC212-induced apoptosis