title: Anti-carcinogenic properties of omeprazole against human colon cancer             cells and azoxymethane-induced colonic aberrant crypt foci formation in rats.
abstract: Omeprazole is a proton pump inhibitor, a widely used drug to treat ulcers             and gastroesophageal refluxdisease. We have evaluated colon cancer chemopreventive             properties of omeprazole using azoxymethane (AOM)-induced colonic aberrant crypt             foci (ACF) in male F344 rats and analyzed cell growth inhibition and apoptosis             induction in human colon cancer cells. Five-week-old male F344 rats were fed a             control or experimental diet containing two doses of omeprazole (200 and 400 ppm).             After one week, all animals were s.c. injected with AOM (15 mg/kg body weight,             once weekly for two weeks). Rats continued on experimental diets for seven more             weeks before being sacrificed. Colons were histopathologically evaluated for ACF.             Human colon cancer HCT-116 and HCA-7 cells treated with omeprazole were evaluated             for different markers associated with proliferation and apoptotic markers using             Western blot technique. Rats fed with 200 and 400 ppm of omeprazole significantly             suppressed total colonic ACF formation (~30%, P<0.001) and showed significant             suppression of multi-crypt foci (~30-50%, P<0.05-0.001). Omeprazole produced             significant dose-response effects on inhibition of multi-crypt foci (≥4). Omeprazole             treatment in human colon cancer cell lines HCT-116 and HCA-7 cells resulted in             induction of p21waf1/cip1 and decreased the expression of anti-apoptotic proteins             Bcl-2, Bcl-XL and survivin in a dose-dependent manner. Anticancer properties observed             in colon cancer cell lines suggest that omeprazole may induce key signaling molecules             of antiproliferation and inhibition of anti-apoptotic proteins.
authors.affiliation: Center for Chemoprevention and Cancer Drug Development, Department                     of Medicine, Hem-Onc Section, PC Stephenson Oklahoma Cancer Center, University                     of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Jagan M R
authors.initials: JM
authors.lastname: Patlolla
authors.forename: Yuting
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Steele
authors.forename: Chinthalapally V
authors.initials: CV
authors.lastname: Rao
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane; D048708:Cell Growth Processes / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D016588:Anticarcinogenic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009853:Omeprazole; D001397:Azoxymethane