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The Prooxidant Action of Dietary Antioxidants Leading to Cellular DNA Breakage and Anticancer Effects: Implications for Chemotherapeutic Action Against Cancer

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Abstract

Plant-derived dietary antioxidants have attracted considerable interest in recent past for their ability to induce apoptosis and regression of tumors in animal models. While it is believed that the antioxidant properties of these agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, it could not account for apoptosis induction and chemotherapeutic observations. In this article, we show that dietary antioxidants can alternatively switch to a prooxidant action in the presence of transition metals such as copper. Such a prooxidant action leads to strand breaks in cellular DNA and growth inhibition in cancer cells. Further, the cellular DNA breakage and anticancer effects were found to be significantly enhanced in the presence of copper ions. Moreover, inhibition of antioxidant-induced DNA strand breaks and oxidative stress by Cu(I)-specific chelators bathocuproine and neocuproine demonstrated the role of endogenous copper in the induction of the prooxidant mechanism. Since it is well established that tissue, cellular, and serum copper levels are considerably elevated in various malignancies, such a prooxidant cytotoxic mechanism better explains the anticancer activity of dietary antioxidants against cancer cells.

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Acknowledgment

The authors acknowledge the financial assistance provided by the University Grants Commission, New Delhi, under the DRS-II program and Junior Research Fellowship to HYK from CSIR, New Delhi.

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

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  1. M. F. Ullah

    Present address: Department of Pathobiology, University of Tenneessee, Knoxville, TN, 37996, USA

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202002, India

    M. F. Ullah, Husain Y. Khan, H. Zubair & S. M. Hadi

  2. Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Aamir Ahmad & Fazlul H. Sarkar

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  1. M. F. Ullah
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Correspondence to S. M. Hadi.

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Ullah, M.F., Ahmad, A., Khan, H.Y. et al. The Prooxidant Action of Dietary Antioxidants Leading to Cellular DNA Breakage and Anticancer Effects: Implications for Chemotherapeutic Action Against Cancer. Cell Biochem Biophys 67, 431–438 (2013). https://doi.org/10.1007/s12013-011-9303-4

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