Fig. 5

Different fates of epidermal growth factor (EGF)-EGF receptor (EGFR) harboring the T790 M mutation in basal and excessive reactive oxygen species (ROS) conditions. a In the basal condition, the EGFR T790 M mutant activates NADPH oxidase 2 (NOX2) to produce ROS, and further oxidizes cysteine (Cys)797 of the EGFR, resulting in mild oxidation of methionine (Met)790. In this condition, basal activity of Met reductase A (MsrA) is fully responsible for reducing the oxidized form of Met790 on the EGFR to the reduced form and protects it from degradation, resulting in cell survival. b Under a condition of sanguinarine-mediated ROS overproduction, a reduction-oxidation reaction (redox) imbalance is induced by activating NOX3 to cause oxidation and depletion of NADPH, resulting in MsrA inactivation and loss of the ability to reduce the oxidized form of Met790 on the EGFR. Excessive amounts of ROS can further induce overoxidation of Met790 on the EGFR and ultimately induce EGFR degradation and cell apoptosis