672HUHS1015 INDUCES APOPTOSIS OF MKN45 GASTRIC CANCER CELLS BY ACTIVATING CASPASE-3 IN ASSOCIATION WITH MITOCHONDRIAL DAMAGEThe newly synthesized anticancer drug HUHS1015 induced apoptosis of MKN45 poorly differentiated gastric adenocarcinoma cells in a concentration (0.3-100 μM)-dependent manner. HUHS1015 markedly activated caspase-3 without affecting caspase-9 activity in MKN45 cells. HUHS1015 disrupted mitochondrial membrane potentials in MKN45 cells. HUHS1015 did not affect release of cytochrome c, DIABLO, apoptosis inducing factor (AIF), or AIF-homologous mitochondrion-associated inducer of death (AMID) from the mitochondria in MKN45 cells. Taken together, these results indicate that HUHS1015 induces apoptosis of MKN45 cells by activating caspase-3 in association with mitochondrial damage, regardless of cytochrome c/caspase-9, DIABLO, AIF, or AMIDtomoyuki@hyo-med.ac.jpResearch6102015HUHS1015,Gastric cancer,Apoptosis, Caspase-3,MitochondriaMasato Ohyama,Yoshiko Kaku,Ayako Tsuchiya,Takeshi Kanno,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,Division 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