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Mol Nutr Food Res. 2016 Feb;60(2):242-55. doi: 10.1002/mnfr.201500605. Epub 2015 Oct 26.

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

Author information

1
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
2
Departament de Patologia, Facultat de Medicina, Universitat de València, València, Spain.

Abstract

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.

KEYWORDS:

Azoxymethane/dextran sulphate sodium; Chemoprevention; Colitis-associated colorectal cancer; Oleuropein; Th17 response

PMID:
26502315
DOI:
10.1002/mnfr.201500605
[Indexed for MEDLINE]

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