Plant-derived dietary
antioxidants have attracted considerable interest in recent past for their ability to induce apoptosis and regression of
tumors in animal models. While it is believed that the
antioxidant properties of these agents may contribute to lowering the risk of
cancer induction by impeding oxidative injury to
DNA, it could not account for apoptosis induction and chemotherapeutic observations. In this article, we show that dietary
antioxidants can alternatively switch to a prooxidant action in the presence of transition metals such as
copper. Such a prooxidant action leads to strand breaks in cellular
DNA and growth inhibition in
cancer cells. Further, the cellular
DNA breakage and anticancer effects were found to be significantly enhanced in the presence of
copper ions. Moreover, inhibition of
antioxidant-induced
DNA strand breaks and oxidative stress by Cu(I)-specific
chelators bathocuproine and
neocuproine demonstrated the role of endogenous
copper in the induction of the prooxidant mechanism. Since it is well established that tissue, cellular, and serum
copper levels are considerably elevated in various
malignancies, such a prooxidant cytotoxic mechanism better explains the anticancer activity of dietary
antioxidants against
cancer cells.