Cocoa-rich diet prevents azoxymethane-induced colonic preneoplastic lesions in rats by restraining oxidative stress and cell proliferation and inducing apoptosis

Mol Nutr Food Res. 2011 Dec;55(12):1895-9. doi: 10.1002/mnfr.201100363. Epub 2011 Sep 23.


Cocoa is a rich source of bioactive compounds with potential chemopreventive ability but up to date its effectiveness in animal models of colon carcinogenesis has not been addressed. Herein, we investigated the in vivo effect of a cocoa-rich diet in the prevention of azoxymethane (AOM)-induced colon cancer and the mechanisms involved. Our results showed that cocoa feeding significantly reduced AOM-induced colonic aberrant crypt foci formation and crypt multiplicity. Oxidative imbalance in colon tissues seems to be prevented by cocoa as indicated by reduced oxidation markers levels and increased enzymatic and non-enzymatic endogenous defences. Cocoa-rich diet also exhibited antiproliferative effects by decreasing the levels of extracellular regulated kinases, protein kinase B and cyclin D1 together with pro-apoptotic effects evidenced by reduced Bcl-x(L) levels and increased Bax levels and caspase-3 activity. Our findings provide the first in vivo evidence that a cocoa-rich diet may inhibit the early stage of colon carcinogenesis probably by preventing oxidative stress and cell proliferation and by inducing apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Azoxymethane / toxicity
  • Cacao / chemistry*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects*
  • Colon / drug effects
  • Colon / pathology
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / prevention & control*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Diet
  • Gene Expression Regulation
  • Oxidative Stress / drug effects*
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / prevention & control
  • Rats
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Anticarcinogenic Agents
  • Bax protein, rat
  • Ccnd1 protein, rat
  • bcl-2-Associated X Protein
  • Cyclin D1
  • Casp3 protein, rat
  • Caspase 3
  • Azoxymethane