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Metabolic Production of H2O2 in Carcinogenesis and Cancer Treatment

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Redox-Active Therapeutics

Abstract

The metabolic production of O2 •− and H2O2 in the presence of redox active metal ions is known to contribute to several steps involved with initiation, promotion, and progression of carcinogenesis that can induce genomic instability, promotion of the transformed phenotype, and rapid cancer cell growth as well as progression to an aggressively malignant phenotype. However, when the metabolic production of H2O2 can be further increased selectively in cancer vs. normal cells using pharmacological approaches, H2O2 can enhance tumoricidal responses to traditional cancer therapies by selectively increasing metabolic oxidative stress. In this way, the metabolic production of H2O2 can be considered as a double-edged sword that can exert both detrimental and beneficial effects in cancer biology and therapy. This chapter discusses critical mechanistic details surrounding the pleiotropic effects of H2O2-induced metabolic oxidative stress in cancer biology and therapy that could be used to develop novel biochemical rationales for controlling cancer in humans.

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Acknowledgements

The authors thank Drs. Larry Oberley, Garry Buettner, Frederick Domann, Prabhat Goswami, and Joseph Cullen for many helpful scientific discussions. The authors thank Gareth Smith for graphics and manuscript editorial assistance. The authors were supported in part by a grant from ASTRO JF2014-1, The Carver Research Program of Excellence in Redox Biology, P30CA086862, and NIH CA182804.

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  1. Division of Free Radical and Radiation Biology, Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, 200 Hawkins Drive, Iowa City, IA, 52242-1009, USA

    Bryan G. Allen & Douglas R. Spitz

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  1. Bryan G. Allen
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  2. Douglas R. Spitz
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Correspondence to Bryan G. Allen .

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  1. Duke University School of Medicine, Durham, North Carolina, USA

    Ines Batinić-Haberle

  2. Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil

    Júlio S. Rebouças

  3. Duke University School of Medicine, Durham, North Carolina, USA

    Ivan Spasojević

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Allen, B.G., Spitz, D.R. (2016). Metabolic Production of H2O2 in Carcinogenesis and Cancer Treatment. In: Batinić-Haberle, I., Rebouças, J., Spasojević, I. (eds) Redox-Active Therapeutics. Oxidative Stress in Applied Basic Research and Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-30705-3_6

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