587INDUCTION OF APOPTOSIS BY PROTON PUMP INHIBITOR THROUGH A CASPASE-DEPENDENT PATHWAY IN HUMAN COLON CANCER CELLSProton pump inhibitors are the most widely prescribed drugs for the treatment of gastric acid-related diseases, due to their potent ability to suppress gastric acid production. Recent studies suggest that proton pump inhibitors can induce apoptosis in a variety of cancer cells, and an emerging concept for this anti-tumor effect is their ability to change intracellular acidity in these tumor cells. The purpose of this study is to evaluate the effect of a proton pump inhibitor (omeprazole) on apoptosis in a human colon cancer cell line.Main methods: Caco-2 human colorectal cancer cells were incubated with various concentrations of omeprazole in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and established concentrations resulting in 25% to 50% cell viability were selected for further evaluation. Apoptosis in Caco-2 cells treated with omeprazole at these concentrations was then established using terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling (TUNEL) and 4'-6-diamidino-2-phenylindole (DAPI) staining. Signals related to apoptosis such as caspase-3, caspase-8, Bcl-2, Bax, and PARP expression were then measured using western blot analysis. Key findings: The TUNEL assay showed that omeprazole induced apoptosis in human Caco-2 cells. Expression of the activated forms of major signaling molecules related to apoptosis such as caspase-3, caspase-8 and PARP were significantly increased, and the anti-apoptotic protein Bcl-2 decreased upon treatment with omeprazole. Significant increases in Bax/Bcl-2 expression ratios were also observed in omeprazole-treated cells compared to controls. Significance: These findings demonstrate that application of a proton pump inhibitor induces apoptosis in human colon cancer cells via a caspase-dependent pathway.drchunhj@chol.comresearch632015Colon cancer,Proton pump Inhibitors,Omeprazole,Apoptosis,Caspase-dependen,Colon cancer,Proton pump Inhibitors,Omeprazole,Apoptosis,Caspase-dependentSun Young Kim,Ji Yeon Lim,Hoon Jai Chun,Yoonjin Kim,Hyuk Soon Choi,Eun Sun Kim,Bora Keum,Yeon Seok Seo,Yoon Tae Jeen, Soon Ho Um,Hong Sik Lee,Chang Duck Kim,Ho Sang Ryu,Woon Won Jung,Donggeun Sul Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Seoul, Korea,Graduate School of Medicine, Korea University, Seoul, Korea, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Seoul, Korea,Graduate School of Medicine, Korea University, Seoul, Korea, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Seoul, Korea, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Seoul, Korea, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Seoul, Korea, Division of Gastroenter