Targeting Reactive Oxygen Species in Cancer via Chinese Herbal Medicine

Figure 1

Production, regulation, and biological effects of ROS. Mitochondria and NOXs are the main sources of O₂^⋅-. O₂^⋅- is formed by molecular oxygen that receives one single electron leaking from mitochondrial ETC or from NOXs. O₂^⋅- is then rapidly converted into H₂O₂ by the corresponding SODs. H₂O₂ can be converted into H₂O through intracellular antioxidants such as PRX, GPX, and CAT. When the H₂O₂ level is uncontrollably increased, OH^⋅ is further formed via the Fenton reaction with metal ions, thereby damaging biological macromolecules such as DNA, lipids, and proteins. In addition, H₂O₂ is a major signaling molecule participating in cellular physiological and pathological processes. The effects of ROS depend on their intracellular concentration. Normal cells typically have lower concentrations of ROS due to their normal metabolism; in normal cells, ROS act as signaling molecules to maintain homeostasis, such as by limiting cellular proliferation, differentiation, and survival. The increased metabolic activity of cancer cells produces high concentrations of ROS, leading to a series of tumor-promoting events, such as DNA damage, genomic instability, oncogene activation, sustained proliferation, and survival. Elevated ROS concentrations also result in the protective growth of cancer cells with enhanced antioxidant capacity to maintain tumor-promoting signaling. Increasing ROS levels to the toxicity threshold, such as by treatment with exogenous ROS inducers or antioxidant inhibitors, causes oxidative damage to cells and, inevitably, cell death.