Phytoagents for Cancer Management: Regulation of Nucleic Acid Oxidation, ROS, and Related Mechanisms

Figure 7

Role switches under different conditions—phytoagents function as both antioxidants and prooxidants in concert with transition metal ions. The level of transition metal ions determines whether a phyto-antioxidant ultimately functions as cytoprotective antioxidant or cytotoxic prooxidant. Under normal levels of transition metal ions, phytoantioxidants serve as radical scavengers and Nrf2/ARE activators that confer a cytoprotective effect that can be applied in chemoprevention. When the level of intracellular transition metal ion is high, such as in cancer cells, phytoantioxidants recycle the metal ions and thus facilitate ROS production through the Fenton or Fenton-like reactions. Otherwise, metal ions catalyze the cleavage of phytoagents and generate radical cleavage products that can cause ROS. Such a prooxidant effect further drives the redox-sensitive cancer cells to their antioxidant limit and leads to cytotoxicity that can be applied as a chemotherapeutic strategy. On the other hand, metal-chelating phytoagents reduce metal ion levels and thus block the ROS producing Fenton(-like) reaction and provide a cytoprotective effect.