title: The comparative study of acetyl-11-keto-beta-boswellic acid (AKBA) and aspirin in the prevention of intestinal adenomatous polyposis in APC(Min/+) mice.
abstract: Acetyl-11-keto-beta-BA (AKBA), a component of the gum resin of Boswellia serrata, has been recognized as a promising agent for the prevention of intestinal tumorigenesis. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), has also been considered to have the activity against intestinal tumorigenesis. However, the prevention of colonic cancer is insufficient and no definitive recommendation has been made for clinic use. Herein, we compared the efficacy of AKBA with that of aspirin in an adenomatous polyposis coli intestinal neoplasia consecutive weeks. Mice were sacrificed by anesthetizing. The whole intestine was removed from each mouse. The number, size and histopathology of intestinal adenomatous polyps were examined under microscopy. The adenomatous polyps were removed for further analysis by the assays of western blotting and immunohistochemical staining. AKBA significantly prevented the formation of intestinal adenomatous polyps without toxicity to mice. Statistical analysis indicated that AKBA's activity both in the prevention of small intestinal and colonic polyps was more potently than aspirin. Histopathologic examination revealed that AKBA's effect, that is the reduction of polyp size and degree of dysplasia, was more prominent in larger sized polyps, especially those originating in colon. These effects of AKBA were associated with its role in the induction of apoptosis in carcinomas. The assays of western blotting and immunohistochemistry staining indicated that the efficacy of AKBA might arise from its activity in the modulation of the Wnt/β-catenin pathway and NF-κB/COX-2 pathway in adenomatous polyps. Conclusion, AKBA by oral application prevented intestinal tumorigenesis more potential than aspirin.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University.
authors.forename: Ruiqi
authors.initials: R
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zuhua
authors.initials: Z
authors.lastname: Gao
authors.forename: Xianjun
authors.initials: X
authors.lastname: Qu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D017491:Genes, APC; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D013997:Time Factors; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; C495267:CTNNB1 protein, mouse; D018836:Inflammation Mediators; D016328:NF-kappa B; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; D051176:beta Catenin; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D001241:Aspirin