Cancer Research Journal

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Copper Enhances Antitumor Activity of Water Soluble Garlic Extract Components on a Human Hepatoma Cell Line

Received: 03 August 2016    Accepted: 31 August 2016    Published: 21 September 2016
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Abstract

Water garlic extract combined with Copper (GE-Cu) shows specific anti-proliferative and antitumoral activity in human hepatocarcinoma (HepG2) cancer cell line, while it is not active on differentiated or primary isolated cells, normal human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK). Since other transition metals do not affect cell viability, the observed antineoplastic property, was found specific for copper (Cu), and atomic absorption analyses demonstrate an accumulation of this metal inside the cell nuclei. GE-Cu treatment of HepG2a cancer cells, induces cell differentiation, growth arrest and programmed cell death. Furthermore, GE-Cu produces a continuous and prolonged flux of oxidative radicals, which down-regulates nuclear antioxidant defenses and repair systems, thus generating direct double-strand breaks to DNA. Indeed, it was observed that in GE-Cu-treated HepG2 cancer cells, histone deacetylase (HDAC) is inhibited, and histone H2AX is early phospho-activated. DNA double strand break downstream, likely responsible for the observed cell death in HepG2 cell, was evidenced by an early over expression of p53 and p21. JNK/c-Jun and p-38 phosphorylative cascade are activated as response to oxidative stress also. The resulting apoptosis appears to be caspases-independent because, under our experimental conditions, nuclear translocation of the apoptosis inducing factor (AIF) is operative. Our data suggest that GE-Cu possess an active specific antitumor capability, which could provide valuable new tools in cancer prevention and in supporting traditional chemotherapy.

DOI 10.11648/j.crj.20160405.12
Published in Cancer Research Journal (Volume 4, Issue 5, September 2016)
Page(s) 73-83
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Garlic, Copper, p-Jun, HDAC, Apoptosis, HepG2

References
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Author Information
  • Department of Biology, University of Rome “Tor Vergata”, Rome, Italy

  • Botany Department, Faculty of Science, Alexandria University, Alexandria, Egypt

  • Department SPES, University of Molise, Campobasso, Italy

  • Department of Science, People’s Friendship University of Russia, Moscow, Russia

  • Department of Biology, University of Rome “Tor Vergata”, Rome, Italy

  • Department of Biology, University of Rome “Tor Vergata”, Rome, Italy

Cite This Article
  • APA Style

    Angelo De Martino, Hanan Mahmoud Abu-Zeid, Piera Torricelli, Anna Shevchenko, Alberto Siciliano, et al. (2016). Copper Enhances Antitumor Activity of Water Soluble Garlic Extract Components on a Human Hepatoma Cell Line. Cancer Research Journal, 4(5), 73-83. https://doi.org/10.11648/j.crj.20160405.12

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    ACS Style

    Angelo De Martino; Hanan Mahmoud Abu-Zeid; Piera Torricelli; Anna Shevchenko; Alberto Siciliano, et al. Copper Enhances Antitumor Activity of Water Soluble Garlic Extract Components on a Human Hepatoma Cell Line. Cancer Res. J. 2016, 4(5), 73-83. doi: 10.11648/j.crj.20160405.12

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    AMA Style

    Angelo De Martino, Hanan Mahmoud Abu-Zeid, Piera Torricelli, Anna Shevchenko, Alberto Siciliano, et al. Copper Enhances Antitumor Activity of Water Soluble Garlic Extract Components on a Human Hepatoma Cell Line. Cancer Res J. 2016;4(5):73-83. doi: 10.11648/j.crj.20160405.12

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  • @article{10.11648/j.crj.20160405.12,
      author = {Angelo De Martino and Hanan Mahmoud Abu-Zeid and Piera Torricelli and Anna Shevchenko and Alberto Siciliano and Simone Beninati},
      title = {Copper Enhances Antitumor Activity of Water Soluble Garlic Extract Components on a Human Hepatoma Cell Line},
      journal = {Cancer Research Journal},
      volume = {4},
      number = {5},
      pages = {73-83},
      doi = {10.11648/j.crj.20160405.12},
      url = {https://doi.org/10.11648/j.crj.20160405.12},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.crj.20160405.12},
      abstract = {Water garlic extract combined with Copper (GE-Cu) shows specific anti-proliferative and antitumoral activity in human hepatocarcinoma (HepG2) cancer cell line, while it is not active on differentiated or primary isolated cells, normal human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK). Since other transition metals do not affect cell viability, the observed antineoplastic property, was found specific for copper (Cu), and atomic absorption analyses demonstrate an accumulation of this metal inside the cell nuclei. GE-Cu treatment of HepG2a cancer cells, induces cell differentiation, growth arrest and programmed cell death. Furthermore, GE-Cu produces a continuous and prolonged flux of oxidative radicals, which down-regulates nuclear antioxidant defenses and repair systems, thus generating direct double-strand breaks to DNA. Indeed, it was observed that in GE-Cu-treated HepG2 cancer cells, histone deacetylase (HDAC) is inhibited, and histone H2AX is early phospho-activated. DNA double strand break downstream, likely responsible for the observed cell death in HepG2 cell, was evidenced by an early over expression of p53 and p21. JNK/c-Jun and p-38 phosphorylative cascade are activated as response to oxidative stress also. The resulting apoptosis appears to be caspases-independent because, under our experimental conditions, nuclear translocation of the apoptosis inducing factor (AIF) is operative. Our data suggest that GE-Cu possess an active specific antitumor capability, which could provide valuable new tools in cancer prevention and in supporting traditional chemotherapy.},
     year = {2016}
    }
    

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  • TY  - JOUR
    T1  - Copper Enhances Antitumor Activity of Water Soluble Garlic Extract Components on a Human Hepatoma Cell Line
    AU  - Angelo De Martino
    AU  - Hanan Mahmoud Abu-Zeid
    AU  - Piera Torricelli
    AU  - Anna Shevchenko
    AU  - Alberto Siciliano
    AU  - Simone Beninati
    Y1  - 2016/09/21
    PY  - 2016
    N1  - https://doi.org/10.11648/j.crj.20160405.12
    DO  - 10.11648/j.crj.20160405.12
    T2  - Cancer Research Journal
    JF  - Cancer Research Journal
    JO  - Cancer Research Journal
    SP  - 73
    EP  - 83
    PB  - Science Publishing Group
    SN  - 2330-8214
    UR  - https://doi.org/10.11648/j.crj.20160405.12
    AB  - Water garlic extract combined with Copper (GE-Cu) shows specific anti-proliferative and antitumoral activity in human hepatocarcinoma (HepG2) cancer cell line, while it is not active on differentiated or primary isolated cells, normal human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK). Since other transition metals do not affect cell viability, the observed antineoplastic property, was found specific for copper (Cu), and atomic absorption analyses demonstrate an accumulation of this metal inside the cell nuclei. GE-Cu treatment of HepG2a cancer cells, induces cell differentiation, growth arrest and programmed cell death. Furthermore, GE-Cu produces a continuous and prolonged flux of oxidative radicals, which down-regulates nuclear antioxidant defenses and repair systems, thus generating direct double-strand breaks to DNA. Indeed, it was observed that in GE-Cu-treated HepG2 cancer cells, histone deacetylase (HDAC) is inhibited, and histone H2AX is early phospho-activated. DNA double strand break downstream, likely responsible for the observed cell death in HepG2 cell, was evidenced by an early over expression of p53 and p21. JNK/c-Jun and p-38 phosphorylative cascade are activated as response to oxidative stress also. The resulting apoptosis appears to be caspases-independent because, under our experimental conditions, nuclear translocation of the apoptosis inducing factor (AIF) is operative. Our data suggest that GE-Cu possess an active specific antitumor capability, which could provide valuable new tools in cancer prevention and in supporting traditional chemotherapy.
    VL  - 4
    IS  - 5
    ER  - 

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