GCLC and cancer: Considering the fact that high GCLC or GCLM levels are found in patients with various cancers [40, 41] and that the reduction of GSH production by the irreversible GCL inhibitor promotes apoptosis and attenuates cell growth in cancer cells [42], we speculate that apatinib may also function as a ROS inducer by suppressing the VEGFR2-Nrf2 path, leading to decreased GCLC and GCLM levels, resulting in the reduction of GSH.