Pristimerin, a naturally occurring triterpenoid, attenuates tumorigenesis in experimental colitis-associated colon cancer

Background: Pristimerin is a quinonemethide triterpenoid with anti-cancer, anti-angiogenic, anti-inflammatory and anti-protozoal activity. However, the therapeutic role of pristimerin in colitis-associated colorectal carcinogenesis is unknown. Purpose: We sought to examine the therapeutic effects of pristimerin on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). The goal was to identify the potential mechanism of action underlying the pharmacological activity of pristimerin. Methods: BALB/c mice were injected with AOM and administered 2% DSS in drinking water. The mice were fed with a diet supplemented with pristimerin (1 to 5 ppm), and colonic tissue was collected at 64 days. The inflammatory status of the colon was assessed by determining the levels of cyclooxygenase-2, inducible nitric oxide synthase and pro-inflammatory cytokines using Western blotting, immunohistochemistry and real-time RT-PCR analyses. Markers of proliferation (proliferating cell nuclear antigen) and apoptosis (TUNEL) were identified in the colon tissues immunohistochemically. The levels of cell cycle-, apoptosis-, and signaling-related proteins were detected by Western blot in colon tissues. Results: Administration of pristimerin significantly reduced the formation of colonic tumors. Western blot and immunohistological analyses revealed that dietary pristimerin markedly reduced NF-kappa B-positive cells and levels of inflammation-related proteins in colon tissue. Pristimerin also reduced cell proliferation, induced apoptosis, and decreased the phosphorylation of AKT and FOXO3a in colon tissue. Conclusion: Pristimerin administration decreased inflammation and proliferation induced by AOM/DSS in colon tissue. It also induced apoptosis and regulated the AKT/FOXO3a signaling pathway. Overall, this study indicates the potential value of pristimerin in suppressing colon tumorigenesis.