Resveratrol acts as a Topoisomerase II poison: effects on DNA damage and chromosome stability

"\"In the last years a great interest has emerged on the Resveratrol (RSV) activity in the prevention of various pathologies including cancer.. We recently showed that RSV acts as a Topoisomerase II (TOPO2) poison in glioma cells. TOPO2 is mainly active in proliferating cells and is involved in the resolution of DNA supercoiled and in chromosomes segregation during mitosis. . Here we present data on the effects of RSV in CHO-K1 cells concerning chromosome damage and segregation as a consequence of TOPO2 poisoning. We show an increase in DNA double-strand breaks, measured by Micronucleus Assay (MN), as a consequence of the stabilization of the covalent complex DNA-TOPO2. We show also that MN generated by RSV treatment are positive for the presence of centromere, indicating an aneugenic activity of RSV. The poisoning of TOPO2 can lead to an improper chromosome segregation, demonstrated through an increase of polyploid and endoreduplicated cells. Furthermore since the incomplete segregation can also affect the normal distribution of mitotic figures, we checked mitosis progression showing an increase in metaphases in relation to ana-telophases after RSV treatment.. In a second time we moved attention toward non-proliferating cells, such as Peripheral Blood Mononuclear Cells (PBMC), in order to confirm that the clastogenic and aneugenic effects of RSV are due to the poisoning of TOPO2, normally not expressed in quiescent cells.. On the whole our data show that RSV affects chromosome stability and segregation in proliferating cells; conversely we didn’t observe any effects on DNA damage in non-proliferating cells so supporting the hypothesis to use this molecule as an adjuvant in conventional cancer treatment.\"