Shedding light on the interaction of polydatin and resveratrol with G-quadruplex and duplex DNA: a biophysical, computational and biological approach.
Among polyphenols, trans-resveratrol (tRES) and trans-polydatin (tPD) exert multiple biological effects, particularly antioxidant and antiproliferative. In this work, we have investigated the interaction of tPD with three cancer-related DNA sequences able to form G-quadruplex (G4) structures, as well as with a model duplex, and compared its behaviour with tRES. Interestingly, fluorescence analysis evidenced the ability of tPD to bind all the studied DNA systems, similarly to tRES, with tRES displaying a higher ability to discriminate G4 over duplex with respect to tPD. However, neither tRES nor tPD produced significant conformational changes of the analyzed DNA upon binding, as determined by CD-titration analysis. Computational analysis and biological data confirmed the biophysical results: indeed, molecular docking evidenced the stronger interaction of tRES with the promoter of c-myc oncogene, and immunoblotting assays revealed a reduction of c-myc expression, more effective for tRES than tPD. Furthermore, in vitro assays on melanoma cells proved that tPD was able to significantly reduce telomerase activity, and inhibit cell proliferation, with tRES producing higher effects than tPD.
['Platella|Chiara|C|', 'Raucci|Umberto|U|', 'Rega|Nadia|N|', "D'Atri|Stefania|S|", 'Levati|Lauretta|L|', 'Roviello|Giovanni N|GN|', 'Fuggetta|Maria Pia|MP|', 'Musumeci|Domenica|D|', 'Montesarchio|Daniela|D|']
D017209:Apoptosis D045744:Cell Line, Tumor D049109:Cell Proliferation D004247:DNA D054856:G-Quadruplexes D005960:Glucosides D006801:Humans D008958:Models, Molecular D008968:Molecular Conformation D016271:Proto-Oncogene Proteins c-myc D000077185:Resveratrol D013057:Spectrum Analysis D013267:Stilbenes D013329:Structure-Activity Relationship
G-quadruplex Melanoma cells trans-polydatin and trans-resveratrol