ROS Modulation by Iron Chelators and Lipids: A Developing Anticancer Strategy

This chapter demonstrates that ROS production can be both pro-oncogenic and anti-oncogenic. Beyond the dependence on a specific cancer type, the role played by ROS production depends on its ability to mediate proliferation through signaling vis a vis its cancer cell cytotoxicity. Iron chelators are generally considered as inhibitors of ROS production because they can neutralize the metal as a ROS production catalyst in the Fenton reaction. However, partial iron binding by tridentate and bidentate chelators can leave unbound coordinates on the metal, thus activating its prooxidant capacity and enhancing ROS production. Thus, iron chelators can serve as anticancer agents by inhibiting ROS-mediated oncogenic signaling, but might also curb ROS cancer toxicity thus acting as pro-oncogenic agents. A special kind of cancer cell death, termed ferroptosis, is caused by cancer cell selective iron-mediated ROS production and can be mediated by iron chelators only if they enhance ROS production, either directly or as a rebound effect.