Prooxidant anticancer activity of plant-derived polyphenolic compounds: An underappreciated phenomenon

The disease-preventive benefits of many natural agents, particularly dietary compounds, have been attributed to their well-recognized activity as regulators of the redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that several of these agents can elicit prooxidant behavior that has been linked to their anticancer effects. More than a decade ago, our team demonstrated the prooxidant anticancer effects of several such natural compounds. We proposed that dietary natural products, particularly plant-derived polyphenolic compounds, can take advantage of the elevated copper levels in the tumor microenvironment and promote reactive oxygen species generation, leading to cancer cell-selective DNA damage. Over the last decade, we have proven this hypothesis in cell-free, cellular, and animal tumor models. Our studies highlight an important yet underappreciated role of natural dietary compounds as prooxidants that can have therapeutic significance.