Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats

  • Authors:
    • Jagan M.R. Patlolla
    • Yuting Zhang
    • Qian Li
    • Vernon E. Steele
    • Chinthalapally V. Rao
  • View Affiliations

  • Published online on: Wednesday, September 28, 2011
  • Pages: 170-175
  • DOI: 10.3892/ijo.2011.1214

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.
Journal Cover

January 2012
Volume 40 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Patlolla, J., Zhang, Y., Li, Q., Steele, V., & Rao, C. (2012). Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats. International Journal of Oncology, 40(1), 170-175.
MLA
Patlolla, Zhang, Li, Steele, and Chinthalapally Rao. "Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats." International Journal of Oncology International Journal of Oncology 40.1 (2012): 170-175.
Chicago
Patlolla, Zhang, Li, Steele, and Chinthalapally Rao. "Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats." International Journal of Oncology International Journal of Oncology 40 no. 1 (2012): 170-175.