Stagos Demetrios, Kazantzoglou Georgios, Magiatis Prokopios, Mitaku Sofia, Anagnostopoulos Konstantinos, Kouretas Demetrios
Department of Biochemistry and Biotechnology, University of Thessaly, GR-41221 Larissa, Greece.
Int J Mol Med. 2005 Jun;15(6):1013-22.
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.
近年来，许多报告显示葡萄提取物和葡萄酒对多种癌症如乳腺癌、肺癌和胃癌具有抗癌活性。这种特性主要归因于葡萄中鉴定出的植物多酚。本研究的目的是探讨葡萄提取物及其所含植物多酚发挥化学预防和抗肿瘤活性的机制。因此，使用两种体外试验对来自希腊两个酿酒葡萄品种的水提取物和甲醇提取物、这些提取物中富含多酚的馏分以及葡萄中发现的多酚类物质（咖啡酸、阿魏酸、没食子酸、原儿茶酸和芦丁）进行了筛选：i）拓扑异构酶I松弛试验和ii）丝裂霉素C诱导的DNA链断裂试验。葡萄提取物、富含多酚的馏分以及一些多酚类物质（咖啡酸和原儿茶酸）是拓扑异构酶I的有效抑制剂，这表明对该酶的抑制可能是这些化合物抗癌活性的作用机制之一。此外，葡萄提取物抑制了丝裂霉素C诱导的DNA链断裂，表明它们可以预防活性氧介导的DNA损伤。另一方面，富含多酚的馏分和植物多酚增强了丝裂霉素C诱导的DNA链断裂，表明具有促氧化活性。因此，有趣的是，完整的葡萄提取物通过抑制拓扑异构酶I和丝裂霉素C诱导的DNA损伤而作为化学预防剂，而富含多酚的馏分和植物多酚发挥促氧化活性，导致DNA损伤增强，这可能解释了植物多酚对癌细胞的细胞毒性和诱导凋亡特性。
