Abstract 234: Chemopreventive activity of BioBran/MGN-3, an arabinoxylan from rice bran, against chemical induction of gastric dysplasia and adenocarcinoma in rats

Abstract

Abstract Objective: Gastric cancer is the second leading cause of cancer-related mortality worldwide, suggesting the need to find new modalities to combat this disease. BioBran/MGN-3 contains an arabinoxylan from rice bran, a polysaccharide containing β-1,4-xylopyronase hemicelluloses. Earlier studies showed that BioBran/MGN-3 is a potent biological response modifier, anti-oxidizing agent and inducer of apoptosis in cancer cells. This study evaluated the use of BioBran/MGN-3 in the prevention of gastric cancer in rats and elucidated the mechanisms behind its action. Materials and Methods: N- methyl-N-nitro-N-nitrosoguanidine (MNNG) was orally administered daily to rats for 2 weeks followed by NaCl once every 3 days for 4 weeks. Rats were also given BioBran/MGN-3 daily for a total of 33 weeks. Histopathology, body and organs weight, redox markers were evaluated and the expression of Ki-67 and the apoptosis/proliferation ratio of gastric tissues were also determined. Results: Histopathological examination of MNNG-treated rats showed 9/10 (90%) of the gastric tissues had dysplasia and adenocarcinoma. Among these tissues, 70% showed dysplasia and 20% showed adenocarcinoma. Conversely, rats treated with MNNG plus BioBran/MGN-3 showed lower incidences of dysplasia and adenocarcinoma (41.6%) (p<0.05). Among these tissues, 33.3% (p<0.05) showed dysplasia, and 8.3% showed gastric carcinoma. BioBran/MGN-3 protected against the loss of body, liver and spleen weights due to treatment with MNNG. MNNG caused marked elevation in total free radicals, MDA levels and suppression in the antioxidant levels of GSH, SOD, CAT and GPx. Also, it decreased the levels of total antioxidant capacity in both blood and stomach tissue. In contrast, BioBran/MGN-3 counteracted free radicals, up-regulated the redox status, down regulated Ki-67 expression and markedly increased the apoptosis/proliferation ratio. BioBran/MGN-3 treated rats displayed normal life activity patterns. Conclusion: BioBran/MGN-3 exhibited a significant chemopreventive activity against the progression of gastric cancer by a mechanisms that involve its ability to protect against oxidative stress, to inhibit cell proliferation and to induce apoptosis. Our study suggests BioBran/MGN-3 is a non-toxic agent and may be an effective adjuvant for the treatment of gastric cancers. BioBran/MGN-3 was provided by Daiwa Pharm. Ltd. Tokyo, Japan. Citation Format: Nariman K. Badr El-Din, Salma M. Abdel Fattah, Deyu Pan, Lucilene Tolentino, Mamdooh Ghoneum. Chemopreventive activity of BioBran/MGN-3, an arabinoxylan from rice bran, against chemical induction of gastric dysplasia and adenocarcinoma in rats. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 234. doi:10.1158/1538-7445.AM2014-234