Prooxidant activity of resveratrol in the presence of copper ions: mutagenicity in plasmid DNA.
Resveratrol, a polyphenolic compound of plant origin, has been of much interest to researchers because of its anticancer and cardiovascular properties. Although antioxidant action of this compound is believed responsible for its reported properties, it has also been shown to exhibit prooxidant properties, especially in the presence of copper ions. Here we report the mutagenicity of resveratrol in plasmid DNA. Plasmid bluescript SK(+) DNA was treated with increasing concentrations of resveratrol in the presence and absence of copper ions, transformed into competent DH5alpha cells and sequenced. We looked for mutations caused by resveratrol treatment by comparing the sequences of treated plasmids versus control (untreated plasmid). The results show a decrease in the transformation efficiency of the plasmid after resveratrol treatment, and although all types of mutations were recorded, point mutations (deletions/substitutions) were found to be the predominant ones. Resveratrol alone resulted in deletion of mainly guanine bases. Since copper ions are known to be found in the nucleus, bound to guanine bases in chromatin, our results suggest mobilization of such endogenous copper by resveratrol resulting in prooxidant DNA cleavage at the site. Concentration of copper is reported to be elevated in various malignancies and the present studies might explain the reported anticancer activity of resveratrol in various cancer cell lines.
Ahmad
Aamir
A
Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, UP 202002, India. ahmada@mail.nih.gov
Syed
Farhan Asad
FA
Singh
Saurabh
S
Hadi
S M
SM
D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004249:DNA Damage / Q000187:drug effects; D004252:DNA Mutational Analysis; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D017353:Gene Deletion; D006147:Guanine / Q000737:chemistry; D007763:Lac Operon / Q000235:genetics; D009153:Mutagens; D016877:Oxidants; D010957:Plasmids / Q000187:drug effects* / Q000235:genetics*; D000077185:Resveratrol; D013050:Spectrometry, Fluorescence; D013267:Stilbenes / Q000633:toxicity*
D000972:Antineoplastic Agents, Phytogenic; D009153:Mutagens; D016877:Oxidants; D013267:Stilbenes; D006147:Guanine; D003300:Copper; D004247:DNA; D000077185:Resveratrol