HNE and cholesterol oxidation products in colorectal inflammation and carcinogenesis

Free Radic Biol Med. 2017 Oct:111:186-195. doi: 10.1016/j.freeradbiomed.2017.01.017. Epub 2017 Jan 13.

Abstract

Consistent experimental data suggest the importance of inflammation-associated oxidative stress in colorectal cancer (CRC) pathogenesis. Inflammatory bowel disease with chronic intestinal inflammation is now considered a precancerous condition. Oxidative stress is an essential feature of inflammation. Activation of redox-sensitive pro-inflammatory cell signals and inflammatory mediators concur to establish a pro-tumoral environment. In this frame, lipid oxidation products, namely 4-hydroxynonenal and oxysterols, can be produced in big quantity so as to be able to exert their function as inducers of cell signaling pathways of proliferation and survival. Notably, an important source of these two compounds is represented by a high fat diet, which is undoubtedly a risk factor for inflammation and CRC development. Current evidence for the emerging implication of these two oxidized lipids in inflammation and CRC development is discussed in this review.

Keywords: 4-Hydroxynonenal; Antioxidant response; CRC; Colon; IBD; Intestinal; Oxysterols; Survival.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism*
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology
  • Cholesterol / metabolism
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Diet, High-Fat / adverse effects
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inflammation
  • Inflammatory Bowel Diseases / etiology
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / pathology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Oxysterols / metabolism*
  • Risk Factors
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • Aldehydes
  • NF-kappa B
  • Oxysterols
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Cholesterol
  • 4-hydroxy-2-nonenal