title: Chemopreventive Activity of MGN-3/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer Cells.
abstract: In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer.
authors.affiliation: Department of Zoology, Faculty of Science, University of Mansoura, Mansoura, Egypt na_ri_eg@yahoo.com.
authors.forename: Nariman K
authors.initials: NK
authors.lastname: Badr El-Din
authors.affiliation: National Center for Radiation and Technology, Cairo, Egypt.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Abdel Fattah
authors.affiliation: Charles Drew University of Medicine and Science, Los Angeles, CA, USA.
authors.forename: Deyu
authors.initials: D
authors.lastname: Pan
authors.affiliation: Charles Drew University of Medicine and Science, Los Angeles, CA, USA.
authors.forename: Lucilene
authors.initials: L
authors.lastname: Tolentino
authors.affiliation: Charles Drew University of Medicine and Science, Los Angeles, CA, USA.
authors.forename: Mamdooh
authors.initials: M
authors.lastname: Ghoneum
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D063646:Carcinogenesis / Q000139:chemically induced* / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D014990:Xylans / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D014990:Xylans; D051028:bcl-2-Associated X Protein; C419427:polysaccharide MGN3; D008769:Methylnitronitrosoguanidine; C085118:arabinoxylan; D053148:Caspase 3
keywords: Biobran; adenocarcinoma; chemopreventive; dysplasia; gastric cancer