Tumor Biology

, Volume 36, Issue 2, pp 1237–1244 | Cite as

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

  • Sayeed Ur Rehman
  • Haseeb Zubair
  • Tarique Sarwar
  • Mohammed Amir Husain
  • Hassan Mubarak Ishqi
  • Shamshun Nehar
  • Mohammad Tabish
Research Article

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.

Keywords

6-mercaptopurine Copper Proxidant property DNA damage Comet assay 

Notes

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.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Sayeed Ur Rehman
    • 1
  • Haseeb Zubair
    • 1
  • Tarique Sarwar
    • 1
  • Mohammed Amir Husain
    • 1
  • Hassan Mubarak Ishqi
    • 1
  • Shamshun Nehar
    • 2
  • Mohammad Tabish
    • 1
  1. 1.Department of Biochemistry, Faculty of Life SciencesA. M. UniversityAligarhIndia
  2. 2.PG Section, Department of ZoologyRanchi UniversityRanchiIndia

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