Effects of curcumin on dna damage, cell proliferation, and incidence of gastric cancer induced by high salt and n-methyl-n-nitrosourea in rats

Abstract

Gastric cancer can generate in any part of the stomach. Because of poorly detected, gastric cancer causes the public health problem worldwide. Curcumin has anti-oxidant and chemopreventive properties. To determine whether curcumin could attenuate the gastric cancer incidence and the key proteins involved in carcinogenesis induced by saturated salt (s-NaCl) and N-methyl-N-nitrosourea (MNU) in rats. Male Wistar rats were divided into 6 groups: 1 control (CO), 2 control supplemented with 200 mg/kg curcumin (CC), 3 MNU+s-NaCl, 4 MNU+s-NaCl supplemented with 200 mg/kg curcumin daily for the first 3 weeks (MNU+s-NaCl+C3W), 5 MNU+s-NaCl rats supplemented with curcumin after induction (MNU+s-NaCl+C17W), and 6 MNU+s-NaCl supplemented with curcumin for 20 weeks (MNU+s-NaCl+C20W). To induce stomach cancer, rats except for group 1 and 2 were orally treated with 100 mg/kg MNU on day 0 and 14, and s-NaCl twice-a-week for the first 3 weeks. The experiment was finished and rats were sacrificed at the end of 20 weeks. The stomachs were removed for histological examination. The expressions of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and cyclin D1 were investigated by immunohistochemistry. Western blot technique was used to examine phosphorylated inhibitor kappaB alpha (ӀҡB∝), and Bcl-2 expressions Cancers were found in the forestomach of all rats in group 3 and 5. Curcumin supplementations in group 4 and 6 showed 40% and 50% reduction of cancer incidence, respectively. Expressions of 8-OHdG, cyclin D1, and Bcl-2 significantly increased in group 3 compared with group 1. The phospho-ӀҡB∝ expression had a tendency to increase in group 3 compared with group 1. Immunoreactive cells of 8-OHdG in group 5 and 6 significantly decreased when compared with group 3 (46.43% ± 4.42 and 46.38% ± 3.14 vs. 53.06% ± 5.96; p = 0.012 and p = 0.011, respectively). The relative intensity of phospho-ӀҡB∝ in group 4 tended to reduce when compared with group 3. In conclusion, MNU and s-NaCl administrations lead to forestomach cancer and increase of 8-OHdG, cyclin D1, and Bcl-2 expressions in rats. Early supplementation of curcumin could attenuate the incidence of cancer at 50% with the significant reduction of 8-OHdG.