Effects of plant phenolics and grape extracts from Greek varieties of Vitis vinifera on Mitomycin C and topoisomerase I-induced nicking of DNA

In recent years, a number of reports have shown the anticancer activity of grape extracts and wine against various types of cancer such as breast, lung and gastric cancer. This property is mainly attributed to the plant polyphenols identified in grapes. The aim of the present study was to investigate the mechanisms by which grape extracts and plant polyphenols found in them exert their chemopreventive and antitumour activities. Thus, aqueous and methanolic extracts from two Greek varieties of Vitis vinifera, fractions enriched in polyphenols of these extracts and polyphenolics (caffeic acid, ferulic acid, gallic acid, protocatechuic acid and rutin) found in grapes were screened using two in vitro assays: i) the topoisomerase I relaxation assay and ii) the mitomycin C-induced DNA strand breakage. The grape extracts, the polyphenol-rich fractions and some of the polyphenolics (caffeic acid and protocatechuic acid) were potent inhibitors of topoisomerase I, indicating that the inhibition of this enzyme may be one of the mechanisms accounting for the anticancer activity of these compounds. Moreover, the grape extracts inhibited the mitomycin C-induced DNA strand breakage suggesting that they could prevent ROS-mediated DNA damage. On the other hand, the polyphenol-rich fractions and the plant polyphenols enhanced the mitomycin C-induced DNA strand breakage indicating prooxidant activity. Thus, it is of interest that whole grape extracts act as chemopreventive agents by inhibiting topo I and mitomycin C-induced DNA damage, while polyphenol enriched fractions and plant polyphenolics exert prooxidant activity leading to enhancement of DNA damage which may account for the cytotoxic and apoptosis-inducing properties of plant polyphenols against cancer cells.