BioMetals

, Volume 24, Issue 6, pp 1169–1178 | Cite as

Oral administration of copper to rats leads to increased lymphocyte cellular DNA degradation by dietary polyphenols: implications for a cancer preventive mechanism

  • Husain Y. Khan
  • Haseeb Zubair
  • Mohd F. Ullah
  • Aamir Ahmad
  • Sheikh M. Hadi
Article

Abstract

To account for the observed anticancer properties of plant polyphenols, we have earlier proposed a mechanism which involves the mobilization of endogenous copper ions by polyphenols leading to the generation of reactive oxygen species (ROS) that serve as proximal DNA cleaving agents and lead to cell death. Over the last decade we have proceeded to validate our hypothesis with considerable success. As a further confirmation of our hypothesis, in this paper we first show that oral administration of copper to rats leads to elevated copper levels in lymphocytes. When such lymphocytes with a copper overload were isolated and treated with polyphenols EGCG, genistein and resveratrol, an increased level of DNA breakage was observed. Further, preincubation of lymphocytes having elevated copper levels with the membrane permeable copper chelator neocuproine, resulted in inhibition of polyphenol induced DNA degradation. However, membrane impermeable chelator of copper bathocuproine, as well as iron and zinc chelators were ineffective in causing such inhibition in DNA breakage, confirming the involvement of endogenous copper in polyphenol induced cellular DNA degradation. It is well established that serum and tissue concentrations of copper are greatly increased in various malignancies. In view of this fact, the present results further confirm our earlier findings and strengthen our hypothesis that an important anticancer mechanism of plant polyphenols could be the mobilization of intracellular copper leading to ROS-mediated cellular DNA breakage. In this context, it may be noted that cancer cells are under considerable oxidative stress and increasing such stress to cytotoxic levels could be a successful anticancer approach.

Keywords

Cancer chemoprevention Copper EGCG Genistein Polyphenols Prooxidant DNA breakage 

Notes

Acknowledgments

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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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Husain Y. Khan
    • 1
  • Haseeb Zubair
    • 1
  • Mohd F. Ullah
    • 1
    • 2
  • Aamir Ahmad
    • 3
  • Sheikh M. Hadi
    • 1
  1. 1.Department of Biochemistry, Faculty of Life SciencesAligarh Muslim UniversityAligarhIndia
  2. 2.Department of PathobiologyUniversity of TennesseeKnoxvilleUSA
  3. 3.Department of PathologyKarmanos Cancer Institute, Wayne State University School of MedicineDetroitUSA

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