Antitumor activity of resveratrol is independent of Cu(II) complex formation in MCF-7 cell line

作者：Volkart Priscylla Andrade; Gassen Rodrigo Benedetti; Nogueira Bettina Muhlen; Porto Barbara Nery; Vargas Jose Eduardo^*; Souto Andre Arigony^*

来源：Bioorganic & Medicinal Chemistry Letters, 2017, 27(15): 3238-3242.

DOI：10.1016/j.bmcl.2017.06.036

• Copper
• Resveratrol
• MCF-7
• ROS
• Apoptosis

Resveratrol (Rsv) is widely reported to possess anticarcinogenic properties in a plethora of cellular and animal models having limited toxicity toward normal cells. In the molecular level, Rsv can act as a suppressive agent for several impaired signaling pathways on cancer cells. However, Fukuhara and Miyata have shown a non-proteic reaction of Rsv, which can act as a prooxidant agent in the presence of copper (Cu), causing cellular oxidative stress accompanied of DNA damage. After this discovery, the complex Rsv-Cu was broadly explored as an antitumor mechanism in multiples tumor cell lines. The aim of the study is to explore the anticarcinogenic behavior of resveratrol-Cu(II) complex in MCF-7 cell line.
Selectivity of Rsv binding to Cu ions was analyzed by HPLC and UV-VIS. The cells were enriched with concentrations of 10 and 50 mu M CuSO4 solution and treated with 25 mM of Rsv. Copper uptake after enrichment of cells, as its intracellular distribution in MCF-7 line, was scanned by ICP-MS and TEM-EDS. Cell death and intracellular ROS production were determined by flow cytometry.
Different from the extracellular model, no relationship of synergy between Rsv-Cu(II) and reactive oxidative species (ROS) production was detected in vitro. ICP-MS revealed intracellular copper accumulation to both chosen concentrations (0.33 +/- 0.09 and 1.18 +/- 0.13 ppb) but there is no promotion of cell death by Rsv-Cu(II) complex. In addition, significant attenuation of ROS production was detected when cells were exposed to CuSO4 after Rsv treatment, falling from 7.54% of ROS production when treated only with Rsv to 3.07 and 2.72% with CuSO4.
Based on these findings antitumor activity of resveratrol when in copper ions presence, is not mediated by Rsv-Cu complex formation in MCF-7 human cell line, suggesting that the antitumoral reaction is dependent of a cancer cellular model.

• 出版日期2017-8-1