101. Garcinol suppresses inflammation-associated colon carcinogenesis in mice
- Author
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Mei-Ling Tsai, Li-Yu Chiou, Min-Hsiung Pan, Chi-Tang Ho, and Yi-Shiou Chiou
- Subjects
Male ,Azoxymethane ,P70-S6 Kinase 1 ,Hepatitis ,Ribosomal s6 kinase ,chemistry.chemical_compound ,medicine ,Animals ,Anticarcinogenic Agents ,Colitis ,Protein kinase B ,beta Catenin ,Mice, Inbred ICR ,biology ,Kinase ,Terpenes ,Dextran Sulfate ,Wnt signaling pathway ,Neoplasms, Experimental ,medicine.disease ,Lipid Metabolism ,digestive system diseases ,Biochemistry ,chemistry ,Colonic Neoplasms ,Cancer research ,biology.protein ,Inflammation Mediators ,Food Science ,Biotechnology ,Aberrant crypt foci ,Signal Transduction - Abstract
cope Garcinol is a polyisoprenylated benzophenone derivative isolated from the fruit rind of Garcinia indica and has exhibited chemopreventive effects on azoxymethane)-induced colonic aberrant crypt foci in mice. In this study, we investigated whether garcinol protects against dextran sulfate sodium (DSS) induced colitis/inflammation and azoxymethane/DSS-induced inflammation-related colon tumorigenesis in male ICR mice. We also aimed to delineate the possible molecular mechanisms responsible for these effects. Methods and results Treatment with garcinol prevented shortening of the colon length and the formation of aberrant crypt foci and improved the inflammation score in the mouse colon stimulated by DSS. Moreover, administration of garcinol markedly decreased DSS-induced inducible nitric oxide synthase, cyclooxygenase-2, and proliferating cell nuclear antigen protein expression. The dietary administration of garcinol effectively reduced the tumor size and incidence in the mouse colon. Western blot and immunohistochemical analysis revealed that administration of garcinol significantly downregulated cyclooxygenase-2, cyclin D1, and vascular endothelial growth factor expression via inhibition of the extracellular signal-regulated protein kinase 1/2, phosphatidylinositol 3 kinase/Akt/p70 ribosomal S6 kinase, and Wnt/β-catenin signaling pathways. Conclusion Our results suggest that garcinol may merit further clinical investigation as a chemoprophylactic food that helps prevent colitis-associated colon cancer.
- Published
- 2014