A new study has reported that plant polyphenols interact with intracellular copper, leading to DNA breakage and cell death. The study was designed to investigate a mechanism of action by which the plant polyphenols (-)-Epigallocatechin-3-gallate (EGCG), genistein and resveratrol exert anticancer effects. Dietary sources of these polyphenols include green tea (EGCG), soybeans (genistein) and red grapes (resveratrol). The authors previously hypothesized that the mobilization of copper ions by polyphenols leads to the generation of reactive oxygen species that serve as DNA cleaving agents (causing breaks in DNA strands), leading to cell death. The authors have worked to validate this hypothesis over the last decade.

In the current paper, the authors show for the first time that oral administration of copper to rats leads to elevated copper levels in lymphocytes (white blood cells), which make them vulnerable to cell death caused by exposure to plant polyphenols. When lymphocytes with copper overload were isolated and treated with the polyphenols EGCG, genistein and resveratrol, increased DNA breakage was observed. Pretreatment of high copper lymphocytes with a copper chelator (which binds copper ions, removing them from solution) was found to result in less polyphenol-induced DNA degradation. Iron and zinc chelators were ineffective in preventing this DNA breakage. While copper is a vital nutrient, high levels of copper in the blood have been found to be associated with higher risk of breast cancer. Circulating and tissue concentrations of copper are greatly increased in various types of cancer, including breast, prostate, lung and brain. Copper has also been shown to promote angiogenesis in existing cancers. The present study results strengthen the authors' hypothesis that an important anticancer mechanism of plant polyphenols could be the mobilization of copper, leading to cellular DNA breakage. The authors conclude that since cancer cells are by nature under considerable oxidative stress, increasing such stress to cytotoxic levels could be a successful anticancer approach.