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The present study aimed at understanding the mechanism underlying HUHS1015-induced apoptosis of MKN45 gastric cancer and Caco-2 colonic cell, Apoptosis, cancer cell lines.  HUHS1015 apparently reduced presence of mRNA protein of X-linked inhibitor of apoptosis protein (XIAP) in a treatment time Autophagy  (10-60 min)-dependent manner. The reduction of XIAP protein was prevented by the autophagy inhibitors 3-methyladenine and bafilomycin A1.  XIAP knock-down significantly activated caspase-3 and reduced cell viability in MKN45 and Caco-2 cells.  In the flow cytometry using propidium iodide (PI) and annexin V-FITC (AV), XIAP knock-down significantly increased the proportions of PI-positive/AV-negative, PI-negative/AV-positive, and PI-positive/AV-positive cells, which corresponds to primary necrosis, early apoptosis, and late apoptosis/secondary necrosis, respectively, in both the cell lines.  Taken together, the results of the present study indicate that HUHS1015 promotes autophagic XIAP degradation in MKN45 and Caco-2 cells, thereby neutralizing caspase-3 inhibition due to XIAP, to activate caspase-3 and induce apoptosis

HUHS1015 PROMOTES AUTOPHAGIC XIAP DEGRADATION TO INDUCE APOPTOSIS OF GASTROINTESTINAL CANCER CELLS