Copper Enhances Antitumor Activity of Water Soluble Garlic Extract Components on a Human Hepatoma Cell Line
Cancer Research Journal
Volume 4, Issue 5, September 2016, Pages: 73-83
Received: Aug. 3, 2016;
Accepted: Aug. 31, 2016;
Published: Sep. 21, 2016
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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
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.
Angelo De Martino,
Hanan Mahmoud Abu-Zeid,
Copper Enhances Antitumor Activity of Water Soluble Garlic Extract Components on a Human Hepatoma Cell Line, Cancer Research Journal.
Vol. 4, No. 5,
2016, pp. 73-83.
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