Induction of oxidative stress as a mechanism of action of chemopreventive agents against cancer

Br J Cancer. 2008 Apr 8;98(7):1157-60. doi: 10.1038/sj.bjc.6604225. Epub 2008 Feb 5.

Abstract

Prevention is a promising option for the control of cancer. Cellular redox changes have emerged as a pivotal and proximal event in cancer. In this review, we provide a brief background on redox biochemistry, discuss the important distinction between redox signalling and oxidative stress, and outline the 'multiple biological personalities' of reactive oxygen and nitrogen species: at low concentrations they protect the cell; at higher concentrations they can damage many biological molecules, such as DNA, proteins, and lipids; and, as we argue here, they may also prevent cancer by initiating the death of the transformed cell. Nitric oxide-donating aspirin is discussed as an instructive example: it generates a state of oxidative stress through which it affects several redox-sensitive signalling pathways, leading ultimately to the elimination of the neoplastic cell via apoptosis or necrosis. As additional examples, we discuss the chemopreventive n-3 polyunsaturated fatty acids and conventional nonsteroidal anti-inflammatory drugs, which induce cell death through redox changes. We conclude that modulation of redox biochemistry represents a fruitful approach to cancer prevention.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anticarcinogenic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Aspirin / therapeutic use
  • Fish Oils / therapeutic use
  • Humans
  • Models, Biological
  • Neoplasms / metabolism
  • Neoplasms / prevention & control*
  • Nitric Oxide Donors / therapeutic use
  • Oxidative Stress / physiology*
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Fish Oils
  • Nitric Oxide Donors
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Aspirin