DNA breakage induced by piceatannol and copper(II): Mechanism and anticancer properties

Abstract

Abstract. Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene; Pice), found in a variety of plant sources including grapes, red wine, peanuts and rhubarb, is known as a metabolite and analog of Resveratrol (3,5,4'-trihydroxy-trans-stilbene; Res) and has higher bioactivity than Res. To explore the mechanism of DNA damage induced by Pice in the presence of copper (Cu) (II), gel electrophoresis, UV-visible spectroscopy, fluorescence spectroscopy and Fourier transform infrared spectroscopy were used. The results of gel electrophoresis demonstrated that the hydroxyl radical played a critical role in DNA cleavage. Spectroscopy confirmed that the mechanism of DNA cleavage induced by Pice-Cu(II) involves the Haber Weiss and Fenton reactions. Pice chelates with Cu(II) as a bidentate ligand, and the Pice-Cu(II) complex undergoes intramolecular electron transfer to form the semiquinone radical anion and Cu(I), which may be reoxidated by O 2 to form Cu(II) with hydroxyl radical generation. In brief, the formation of the hydroxyl radical and the Cu(II)/Cu(I) redox cycle play a key role in inducing DNA damage. In this process, Pice demonstrated pro-oxidant properties. Oxidative product(s) of Pice, semiquinone, was formed and Cu(I) was reoxidized to Cu(II). The redox cycling of copper generated reactive oxygen species, which induced DNA cleavage, the hallmark of cell apoptosis. The mechanism of DNA breakage induced by Pice-Cu(II) may be a significant pathway through which cancer cells are killed.

Pro-oxidant activity of polyphenols and its implication on cancer chemoprevention and chemotherapy

“…Consistent with such a hypothesis, phenolic acids, including caffeic, chlorogenic and ferulic acids, were effective inducing DNA cleavage in human promyelocytic leukemia HL-60 cells in the presence of Cu(II) ions[69].Other phenolic compounds, such as piceatannol, a stilbene naturally present in grapes (Vitis vinifera, Vitaceae) and rhubarb (Rheum rhabarbarum, Polygonaceae) rhizome, among others, can interact with copper ions in their oxidized forms, Cu(II), promoting the Haber-Weiss and Fenton reactions, that generate ROS, inducing DNA cleavage. As a result of this reaction, piceatannol is transformed into an ortho-quinone, which forms covalent adducts with DNA[70]. Another hypothesis regarding the role of transition metals in the selectivity of prooxidant activity of polyphenols explains that, due to the Warburg effect, cancer cells in many solid tumors have a high level of glycolysis, leading to an acidification of the pH which affects the DNA structure and exposes the chromatin-bound copper to the potential attack of pro-oxidant agents such as resveratrol[71].…”

The synergy of resveratrol and alcohol against Helicobacter pylori and underlying anti‐ Helicobacter pylori mechanism of resveratrol

“…Resveratrol is a redox active molecule which can bind with transition copper ions and reduce it, and then generate ROS in this process, eventually leading to DNA damage (Subramanian et al 2004;Li et al 2012). The antibacterial property of resveratrol against E. coli is mediated by oxidative damage to the cell membrane (Subramanian et al 2014).…”

Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper

“…Human physiological plasma iron and copper total Türk Diyab Obez / Turk J Diab Obes / 2019; 3: 131-136 concentrations (free and bound) range between (11-31 µM) and (14-19 µM), respectively (24). Copper is one of the most redox active metal ions found in cells and is closely associated with chromatin (25). Therefore the analysis of the effect of chemicals and drugs on DNA and proteins, in the presence of iron and copper is very important and interesting for many researchers.…”