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

Angelo De Martino; Hanan Mahmoud Abu-Zeid; Piera Torricelli; Anna Shevchenko; Alberto Siciliano; Simone Beninati

doi:doi:10.11648/j.crj.20160405.12

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

Angelo De Martino, Hanan Mahmoud Abu-Zeid, Piera Torricelli, Anna Shevchenko, Alberto Siciliano, Simone Beninati

Published in Cancer Research Journal (Volume 4, Issue 5)

Received: 3 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.

Published in	Cancer Research Journal (Volume 4, Issue 5)
DOI	10.11648/j.crj.20160405.12
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), 2016. Published by Science Publishing Group

Keywords

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

References

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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://article.sciencepublishinggroup.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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Author Information

Angelo De Martino

Department of Biology, University of Rome “Tor Vergata”, Rome, Italy
Hanan Mahmoud Abu-Zeid

Botany Department, Faculty of Science, Alexandria University, Alexandria, Egypt
Piera Torricelli

Department SPES, University of Molise, Campobasso, Italy
Anna Shevchenko

Department of Science, People’s Friendship University of Russia, Moscow, Russia
Alberto Siciliano

Department of Biology, University of Rome “Tor Vergata”, Rome, Italy
Simone Beninati

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

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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://article.sciencepublishinggroup.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}
}

Copy | Download

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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