Induction of oxidative stress as a mechanism of action of chemopreventive agents against cancer.
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.
Rigas
B
B
Division of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY 11794-5200, USA. basil.rigas@stonybrook.edu
Sun
Y
Y
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000627:therapeutic use; D005395:Fish Oils / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D020030:Nitric Oxide Donors / Q000627:therapeutic use; D018384:Oxidative Stress / Q000502:physiology*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D005395:Fish Oils; D020030:Nitric Oxide Donors; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D001241:Aspirin