Application of topoisomerase assays in the evaluation of natural products as antitumor agents

Abstract

Initially, DNA topoisomerase (topo) inhibitors found clinical applications as antibiotics and cancer chemotherapeutic agents. Recently, we demonstrated that plant flavonoids that inhibit mammalian topo I or topo II might be useful as cancer chemopreventive agents (Constantinou et al., 1995b). Phytochemicals can inhibit DNA topoisomerases in different ways

depending on the mode and the type of enzyme, these can be classified as topo I poisons, topo II poisons, topo I antagonists, or topo II antagonists. Correctly classifying topo inhibitors is critical because it provides an important lead as to whether the plant agent can be useful in chemoprevention or in chemotherapy. We outline below a strategy that was designed to identify and classify topo I and II inhibitors.