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-κB-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.