Schematic diagram showing the mechanism of EGFRBi armed ATC-mediated killing of AT-101 sensitized tumor cells.

<p>AT-101 a Pan-Bcl-2 inhibitor binds to the BH3 binding domain of Bcl-2 and disrupts its interaction with pro-apoptotic family members such as Bax and Bad. Free Bax and Bad re-localizes into the mitochondria where they initiate the mitochondrial apoptosis. Our results demonstrate that tumor cell stimulated aATC can produce IFN-γ that in turn can phosphorylate Stat1. pStat activation results in Bad/Bax mitochondrial localization and induction of apoptosis. IFN-γ itself is a suppressor of anti-apoptotic Bcl-X_L.