Chemopreventive effect of oleuropein in colitis‐associated colorectal cancer in c57bl/6 mice

SCOPE: The main phenolic secoiridoid oleuropein and active constituent from olive tree (Olea europaea, Oleaceae), has demonstrated anti‐inflammatory properties in intestinal inflammation and anti‐tumoral effects in different cancer cells. In this study, we evaluated the chemoprevention of oleuropein in a model of azoxymethane (AOM)/Dextran sulfate sodium (DSS)‐induced colorectal cancer (CRC) in C57BL/6 mice and the modulatory effect on the Th17 response in DSS acute colitis. METHODS AND RESULTS: Oleuropein protected from AOM/DSS‐induced CRC by improving clinical symptoms, disease activity index score as well as suppressed the growth and multiplicity of colonic tumors. Treatment with oleuropein reduced intestinal IL‐6, IFN‐γ, TNF‐α, and IL‐17A concentration, and decreased cyclooxygenase‐2, Bax and proliferating cell nuclear antigen protein expression. Western blot analysis also showed a markedly downregulation of CRC‐related pathways as nuclear factor‐κB (NF‐κB), Wnt/β‐catenin, phosphatidylinositol‐3‐kinase (P3IK)/Akt, and signal transducer and activators of transcription (STAT)3. In DSS acute model, oleuropein inhibited Th17 response, by decreasing CD4⁺Rorγt⁺ IL‐17⁺ IFN‐γ⁺ T‐cell subsets in the lamina propria, as well as IL‐17A and IFN‐γ expression. CONCLUSION: Oleuropein as a dietary supplementation could be a promising protective agent against colitis‐associated CRC.