Resveratrol acts as a topoisomerase II poison in human glioma cells

""Recently, we demonstrated that Resveratrol (RSV), a well known natural stilbene, is able to induce a delay in S progression with a concomitant increase in ?H2AX expression in U87 glioma cells. Furthermore, we showed that it inhibits the ability of recombinant human topoisomerase IIa to decatenate kDNA in vitro. Because proliferating tumor cells express topoisomerases at high levels and these enzymes are important targets of some of the most successful anticancer drugs, we tested whether RSV is able to poison topoisomerase IIa in glioma cells. Then, we monitored the increase of micronuclei in RSV treated U87 cells as a consequence of the conversion of TOPOII\\\/DNA cleavable complexes to permanent DNA damage. Finally, we assayed the ability of RSV in modulating the expression of target proteins involved in DNA damage signalling, namely ATR, ATM, Chk1, Chk2 and ?H2AX. Through a molecular modelling here we show that RSV binds at the TOPOII\\\/DNA interface thus establishing several hydrogen bonds. Moreover, we show that RSV poisons TOPOIIa so inducing DNA damage; ATM, Chk2 and ?H2AX are involved in the DNA damage signalling after RSV treatment.""