Garcinol suppresses inflammation-associated colon carcinogenesis in mice.

Abstract

SCOPE:

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.

• Authors: Mei-Ling Tsai, Yi-Shiou Chiou, Li-Yu Chiou, Chi-Tang Ho, Min-Hsiung Pan
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 58 Issue 9 Pg. 1820-9 (Sep 2014) ISSN: 1613-4133 [Electronic] Germany
• PMID: 24981158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Anticarcinogenic Agents
• Inflammation Mediators
• Terpenes
• beta Catenin
• Dextran Sulfate
• Azoxymethane
• garcinol

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Azoxymethane (toxicity)
• Colitis (chemically induced, complications, drug therapy, metabolism)
• Colonic Neoplasms (drug therapy, etiology, pathology)
• Dextran Sulfate (toxicity)
• Hepatitis (drug therapy)
• Inflammation Mediators (metabolism)
• Lipid Metabolism (drug effects)
• Male
• Mice, Inbred ICR
• Neoplasms, Experimental (chemically induced, drug therapy)
• Signal Transduction (drug effects)
• Terpenes (pharmacology)
• beta Catenin (metabolism)