ROS-Inducing Agents for Cancer Chemotherapy

Reactive oxygen species (ROS) play an essential role in maintaining cellular homeostasis, and levels of ROS are regulated by redox enzymes and reduced factors such as glutathione. Excess levels of ROS can result in DNA and cellular damage which can contribute to development of tumors. Cancer cells exhibit increased metabolic activity and ROS levels compared to normal cells and, with threshold limits, ROS contribute to cancer cell homeostasis and growth. However, treatment of cancer cells with ROS-inducing anticancer agents exceeds the threshold for ROS and this results in activation of multiple cell death pathways which include inhibition of mammalian target of rapamycin (mTOR) signaling and downregulation of specificity protein (Sp) transcription factors Sp1, Sp3, Sp4 and pro-oncogenic Sp-regulated genes. Thus, ROS-inducing drugs represent a highly effective group of mechanism-based agents for individual and combined cancer chemotherapies.