704XIAP IS A TARGET FOR HUHS1015-INDUCED CASPASE-3 ACTIVATION IN CW2 COLONIC CANCER CELLSThe 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 activationtomoyuki@hyo-med.ac.jpResearch6122015HUHS1015,X-linked inhibitor of apoptosis protein,Degradation,Autophagy,Caspase -3Ayako Tsuchiya,Yoshiko Kaku,Tadashi Shimizu,Akito Tanaka,Tomoyuki NishizakiDivision of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan,Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan,Laboratory of Chemical Biology, Advanced Medicinal Research Center, Hyogo University of Health Sciences, Kobe 650-8530, Japan,Laboratory of Chemical Biology, Advanced Medicinal Research Center, Hyogo University of Health Sciences, Kobe 650-8530, Japan,Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan