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


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.


CONCLUSIONS
Oleuropein as a dietary supplementation could be a promising protective agent against colitis-associated CRC.
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
Elisa
E
Giner
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
M Carmen
MC
Recio
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
José Luis
JL
Ríos
Departament de Patologia, Facultat de Medicina, Universitat de València, València, Spain.
José Miguel
JM
Cerdá-Nicolás
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
Rosa María
RM
Giner
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001397:Azoxymethane / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000517:prevention & control; D058504:Th17 Cells / Q000187:drug effects
D016588:Anticarcinogenic Agents; D016207:Cytokines; D057888:Iridoid Glucosides; D039823:Iridoids; C002769:oleuropein; D016264:Dextran Sulfate; D001397:Azoxymethane
Azoxymethane/dextran sulphate sodium; Chemoprevention; Colitis-associated colorectal cancer; Oleuropein; Th17 response