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Redox cycling of Cu(II) by 6-mercaptopurine leads to ROS generation and DNA breakage: possible mechanism of anticancer activity

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Tumor Biology

Abstract

6-Mercaptopurine (6MP) is a well-known purine antimetabolite used to treat childhood acute lymphoblastic leukemia and other diseases. Cancer cells as compared to normal cells are under increased oxidative stress and show high copper level. These differences between cancer cells and normal cells can be targeted to develop effective cancer therapy. Pro-oxidant property of 6MP in the presence of metal ions is not well documented. Redox cycling of Cu(II) to Cu(I) was found to be efficiently mediated by 6MP. We have performed a series of in vitro experiments to demonstrate the pro-oxidant property of 6MP in the presence of Cu(II). Studies on human lymphocytes confirmed the DNA damaging ability of 6MP in the presence of Cu(II). Since 6MP possesses DNA damaging ability by producing reactive oxygen species (ROS) in the presence of Cu(II), it may also possess apoptosis-inducing activity by involving endogenous copper ions. Essentially, this would be an alternative and copper-dependent pathway for anticancer activity of 6MP.

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Acknowledgments

We thank the Council of Scientific and Industrial Research (C.S.I.R.), New Delhi, India, for the award of Senior Research Fellowship to Sayeed Ur Rehman (File no. 09/112(0470)/2011-EMR1). We are also thankful to the Department of Biochemistry, A.M.U. for providing the necessary facilities.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Life Sciences, A. M. University, Aligarh, U.P., 202002, India

    Sayeed Ur Rehman, Haseeb Zubair, Tarique Sarwar, Mohammed Amir Husain, Hassan Mubarak Ishqi & Mohammad Tabish

  2. PG Section, Department of Zoology, Ranchi University, Ranchi, Jharkhand, 834008, India

    Shamshun Nehar

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  1. Sayeed Ur Rehman
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  2. Haseeb Zubair
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Correspondence to Mohammad Tabish.

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Rehman, S.U., Zubair, H., Sarwar, T. et al. Redox cycling of Cu(II) by 6-mercaptopurine leads to ROS generation and DNA breakage: possible mechanism of anticancer activity. Tumor Biol. 36, 1237–1244 (2015). https://doi.org/10.1007/s13277-014-2743-x

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  • DOI: https://doi.org/10.1007/s13277-014-2743-x

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