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.