EDITORIAL Natural Products as Antitumor Agents: Direct Versus Indirect Mechanisms of Activity of Flavonoids1

A variety of natural products are in various stages of pre-clinical and clinical development as antitumor agents in hu-mans. One group of natural products currently undergoing early-phase clinical trials in humans is flavonoids. Flavonoids are benzo-y-pyrone derivatives, which are ubiquitous in plants. Historically, flavonoid-containing preparations have been utilized for the treatment of a variety of human dis-eases. These natural compounds have been reported to have pleiotropic biological effects (7), including binding to and inhibition of the activity of many biological macromolecules such as vital enzymes. In addition, some flavonoids have been reported to bind divalent ions of heavy metals, influence the permeability of cell membranes, and intercalate into DNA, based on structural similarities to nucleosides. Since these bi-ological effects could be deleterious for rapidly metabolizin