XIAP IS A TARGET FOR HUHS1015-INDUCED CASPASE-3 ACTIVATION IN CW2 COLONIC CANCER CELLS
The newly synthesized anticancer drug HUHS1015 drastically activated caspase-3 in CW2 colonic cancer cells, while much lesser activation of caspase-4, -8, and -9 was obtained. HUHS1015 reduced the mRNA and protein levels of X-linked inhibitor of apoptosis protein (XIAP) in a treatment time (10 -60 min)-dependent manner. The effect of HUHS1015 was attenuated by the autophagy inhibitors 3-methyladenine and bafilomycin A1. The results of the present study thus indicate that HUHS1015 stimulates autophagic XIAP degradation in CW2 cells, to reduce intracellular XIAP levels, allowing neutralization of caspase-3 inhibition due to XIAP followed by caspase-3 activation