Glutathione (GSH) is an essential antioxidant responsible for the maintenance of
intracellular redox homeostasis. As tumors outgrow their blood supply and become hypoxic,
their redox homeostasis is challenged by the production of nitric oxide and reactive oxygen
species (ROS). In gliomas, the sustained import of l-cystine via the l-cystine/l-glutamate
exchanger, system xc−, is rate-limiting for the synthesis of GSH. We show that hypoxia
causes a significant increase in NO and ROS but without affecting glioma cell growth. This is …