Pharmaceutical Research

, Volume 27, Issue 6, pp 979–988

Resveratrol Mobilizes Endogenous Copper in Human Peripheral Lymphocytes Leading to Oxidative DNA Breakage: A Putative Mechanism for Chemoprevention of Cancer

  • S. M. Hadi
  • M. F. Ullah
  • A. S. Azmi
  • A. Ahmad
  • U. Shamim
  • H. Zubair
  • H. Y. Khan
Expert Review

DOI: 10.1007/s11095-010-0055-4

Cite this article as:
Hadi, S., Ullah, M., Azmi, A. et al. Pharm Res (2010) 27: 979. doi:10.1007/s11095-010-0055-4

Abstract

Plant polyphenols are important components of human diet, and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring anti-oxidants but also act as pro-oxidants catalyzing DNA degradation in the presence of metal ions such as copper. The plant polyphenol resveratrol confers resistance to plants against fungal agents and has been implicated as a cancer chemopreventive agent. Of particular interest is the observation that resveratrol has been found to induce apoptosis in cancer cell lines but not in normal cells. Over the last few years, we have shown that resveratrol is capable of causing DNA breakage in cells such as human lymphocytes. Such cellular DNA breakage is inhibited by copper specific chelators but not by iron and zinc chelating agents. Similar results are obtained by using permeabilized cells or with isolated nuclei, indicating that chromatin-bound copper is mobilized in this reaction. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and resveratrol to generate reactive oxygen species responsible for DNA cleavage. The results are in support of our hypothesis that anti-cancer mechanism of plant polyphenols involves mobilization of endogenous copper and the consequent pro-oxidant action. Such a mechanism better explains the anti-cancer effects of resveratrol, as it accounts for the preferential cytotoxicity towards cancer cells.

KEY WORDS

cancer comet assay endogenous copper pro-oxidant action resveratrol 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • S. M. Hadi
    • 1
  • M. F. Ullah
    • 1
  • A. S. Azmi
    • 2
  • A. Ahmad
    • 2
  • U. Shamim
    • 1
  • H. Zubair
    • 1
  • H. Y. Khan
    • 1
  1. 1.Department of Biochemistry, Faculty of Life SciencesAligarh Muslim UniversityAligarhIndia
  2. 2.Department of Pathology, Karmanos Cancer InstituteWayne State University School of MedicineDetroitUSA

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