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Cancer

A radical approach to treatment

Nature volume 407, pages 309–311 (2000)Cite this article

Reactive oxygen species are potentially dangerous by-products of cellular metabolism that have direct effects on cell development, growth and survival, on ageing, and on the development of cancer1. They are generated by all aerobic organisms, but their production is a double-edged sword. On the one hand, they seem to be needed for signal-transduction pathways that regulate cell growth2 and reduction– oxidation (redox) status1. But on the other, excessive amounts of these metabolites can start lethal chain reactions, which oxidize and disable structures that are required for cellular integrity and survival1. Many tumour cells seem to have increased rates of metabolism compared with normal cells, which would typically lead to increased numbers of reactive oxygen species. So one way of treating cancer might be to design drugs to target the enzymes that regulate the levels of reactive oxygen species. On page 390 of this issue3, Huang and colleagues provide support for this idea: they find that a compound that kills human leukaemia cells, but spares normal cells, may achieve this by inhibiting such an enzyme.

A higher level of aerobic metabolism — and hence of reactive oxygen species — in tumour cells compared with normal cells would make enzymes in these pathways good candidate drug targets. However, previous attempts to inhibit SODs have not proved clinically useful. For example, ions that successfully compete with O2− to bind to SODs were not specific enough to cancer cells and produced unacceptable levels of damage to normal cells. But Huang et al.3 now show that a group of oestrogen derivatives, of all things, seem to bind to and inhibit SODs, and that — by damaging mitochondria — these compounds induce the suicide of a variety of human leukaemia cells in vitro.

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Figure 1: Inhibition of superoxide dismutases triggers the suicide of leukaemia cells.

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Authors and Affiliations

  1. Departments of Biochemistry and Hematology/ Oncology, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, 38018, Tennessee, USA

    John L. Cleveland & Michael B. Kastan

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  1. John L. Cleveland
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  2. Michael B. Kastan
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Correspondence to John L. Cleveland or Michael B. Kastan.

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Cleveland, J., Kastan, M. A radical approach to treatment. Nature 407, 309–311 (2000). https://doi.org/10.1038/35030277

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