DNA Intercalation, Topoisomerase I Inhibition, and Oxidative Reactions of Polyphenols

摘要

Polyphenols occur naturally in many foods and have a range of biological effects. Although the mechanisms for these effects are not clear, inhibition of metabolic enzymes may be one possible mode of action in the cell. Using a gel electrophoresis method validated in our laboratory we evaluated the effects of several polyphenols on the DNA-maintenance enzyme topoisomerase IB (topo I). This enzyme (along with topoisomerase II) regulates supercoiling of chromosomal DNA and plays a pivotal role in chromosome replication, transcription, recombination, segregation, condensation and repair. In our studies, the flavones and flavonols had the greatest intercalating and poisoning activity. On the other hand, no evidence for DNA intercalation or topo I inhibition was observed with the anthocyan(id)ins we evaluated. Experimental conditions, including pH, ionic strength and the presence of reductants, free radical scavengers, and trace metals may all have an effect on the solution properties and reactivities of the polyphenols. These experimental conditions must be carefully considered when relating results of in vitro studies to potential biological effects in vivo.