Plant polyphenol induced cell death in human cancer cells involves mobilization of intracellular copper ions and reactive oxygen species generation: A mechanism for cancer chemopreventive action

Authors

  • Husain Yar Khan,

    1. Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India
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  • Haseeb Zubair,

    1. Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India
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  • Mohd Faisal,

    1. Department of Pharmacology and Pharmacotherapy, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
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  • Mohd Fahad Ullah,

    1. Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India
    Current affiliation:
    1. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, KSA
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  • Mohd Farhan,

    1. Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India
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  • Fazlul H. Sarkar,

    1. Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
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  • Aamir Ahmad,

    Corresponding author
    1. Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
    • Correspondence: Dr. Aamir Ahmad, Karmanos Cancer Institute, Wayne State University, 707 HWCRC, 4100 John R. Street, Detroit, MI 48201, USA

      E-mail: ahmada@karmanos.org

      Fax: +1-313-576-8389

      Additional corresponding author: Professor Sheikh Mumtaz Hadi,

      E-mail: smhadi@vsnl.com

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  • Sheikh Mumtaz Hadi

    Corresponding author
    1. Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India
    • Correspondence: Dr. Aamir Ahmad, Karmanos Cancer Institute, Wayne State University, 707 HWCRC, 4100 John R. Street, Detroit, MI 48201, USA

      E-mail: ahmada@karmanos.org

      Fax: +1-313-576-8389

      Additional corresponding author: Professor Sheikh Mumtaz Hadi,

      E-mail: smhadi@vsnl.com

    Search for more papers by this author

Abstract

Scope

Anticancer polyphenolic nutraceuticals from fruits, vegetables, and spices are generally recognized as antioxidants, but can be prooxidants in the presence of copper ions. We earlier proposed a mechanism for such activity of polyphenols and now we provide data in multiple cancer cell lines in support of our hypothesis.

Methods and results

Through multiple assays, we show that polyphenols luteolin, apigenin, epigallocatechin-3-gallate, and resveratrol are able to inhibit cell proliferation and induce apoptosis in different cancer cell lines. Such cell death is prevented to a significant extent by cuprous chelator neocuproine and reactive oxygen species scavengers. We also show that normal breast epithelial cells, cultured in a medium supplemented with copper, become sensitized to polyphenol-induced growth inhibition.

Conclusion

Since the concentration of copper is significantly elevated in cancer cells, our results strengthen the idea that an important anticancer mechanism of plant polyphenols is mediated through intracellular copper mobilization and reactive oxygen species generation leading to cancer cell death. Moreover, this prooxidant chemopreventive mechanism appears to be a mechanism common to several polyphenols with diverse chemical structures and explains the preferential cytotoxicity of these compounds toward cancer cells.

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