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

AbstractSCOPE:
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.
AuthorsElisa Giner, M Carmen Recio, José Luis Ríos, José Miguel Cerdá-Nicolás, Rosa María Giner
JournalMolecular nutrition & food research (Mol Nutr Food Res) Vol. 60 Issue 2 Pg. 242-55 (Feb 2016) ISSN: 1613-4133 [Electronic] Germany
PMID26502315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Chemical References
  • Anticarcinogenic Agents
  • Cytokines
  • Iridoid Glucosides
  • Iridoids
  • oleuropein
  • Dextran Sulfate
  • Azoxymethane
Topics
  • Animals
  • Anticarcinogenic Agents (pharmacology)
  • Azoxymethane (toxicity)
  • Cell Proliferation (drug effects)
  • Colitis (chemically induced, complications, drug therapy)
  • Colon (drug effects, metabolism, pathology)
  • Colorectal Neoplasms (etiology, pathology, prevention & control)
  • Cytokines (metabolism)
  • Dextran Sulfate (toxicity)
  • Female
  • Iridoid Glucosides
  • Iridoids (pharmacology)
  • Mice, Inbred C57BL
  • Neoplasms, Experimental (prevention & control)
  • Th17 Cells (drug effects)

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