Chemopreventive role of olive oil in colon carcinogenesis by targeting noncoding RNAs and methylation machinery

Int J Cancer. 2019 Mar 1;144(5):1180-1194. doi: 10.1002/ijc.31837. Epub 2018 Oct 4.

Abstract

Epigenetic therapy induced by dietary components has become a strong interest in the field of cancer prevention. Olive oil, a potent dietary chemopreventive agent, control colon cancer, however, its role in epigenetic therapy remains unclear. Thus, we aimed to investigate the effect of olive oil in a preclinical model of colon cancer by targeting genetic and epigenetic mechanisms. DMH was used to induce colon cancer in rats; while olive oil was given to separate group of rats along with DMH treatment. Tumor burden and incidence in DMH and DMH + olive oil-treated rats was observed by macroscopic examination and histoarchitectural studies. Potent anti-inflammatory, anti-angiogenic and pro-apoptotic activity of olive oil was explored by gene expression and immunohistochemical studies. The effect of olive oil on epigenetic alterations was examined by detecting promoter methylation with MS-HRM and dysregulation of miRNA by TaqMan MicroRNA Assay. We observed that olive oil administration lowered tumor incidence and inhibited the development of tumors in DMH-treated rats. Olive oil markedly decreased the expression of inflammatory and angiogenic markers and restored the expression of pro-apoptotic markers in DMH-treated rats. Furthermore, the inverse relationship between gene expression and DNA methylation, deviant miRNA pattern and miRNA silencing mediated by aberrant DNA methylation was also seen in DMH-treated rats, which was potentially reversible upon olive oil treatment. Our study concludes that olive oil may play a role in the epigenetic therapy by altering NF-κB and apoptotic pathways via targeting noncoding RNAs and methylation machinery that affecting epigenome to prevent colon carcinogenesis.

Keywords: chemoprevention; colon cancer; methylation; miRNA; olive oil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Carcinogenesis / drug effects*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / prevention & control*
  • DNA Methylation / drug effects*
  • DNA Methylation / genetics
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / genetics
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Male
  • MicroRNAs / genetics
  • NF-kappa B / genetics
  • Olive Oil / pharmacology*
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • RNA, Untranslated / genetics*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • NF-kappa B
  • Olive Oil
  • RNA, Untranslated