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

The present study aimed at understanding the mechanism underlying HUHS1015 - induced apoptosis of MKN45 gastric cancer and Ca co - 2 colonic cell, Apoptosis, cancer cell lines. HUHS1015 apparently r educed 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 - methylad enine 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 propo rtions 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.