Induction of autophagy-dependent apoptosis by the survivin suppressant YM155 in prostate cancer cells

In this study, we demonstrated that YM155, a novel survivin suppressant, induced both apoptosis, and autophagy that was shown by conversion of cytosolic-associated protein light chain 3 (LC3I) into autophagosome-associated form (LC3II) and a punctate fluorescence pattern of an ectopic GFP-LC3 protein. The lysosomal inhibitor chloroquine further accumulated YM155-induced LC3II, indicating an increase of autophagic flux. Ectopic expression of survivin significantly attenuated YM155-induced apoptosis and autophagy, whereas suivivin siRNA induced autophagy. Furthermore, inhibition of either early or late events of autophagy attenuated YM155-induced apoptosis, demonstrating that induction of autophagy proceeds apoptosis. In conclusion, suppression of survivin by YM155 induces autophagy-dependent apoptosis, and YM155-induced autophagy plays a pro-apoptotic role thereby unveiling a novel mechanism of YM155 in prostate cancer cells. (C) 2010 Elsevier Ireland Ltd. All rights reserved.