Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations

Figure 4

Vitamin C is oxidized in the extracellular space to dehydroascorbate (DHA) that is taken up by cancer cells via glucose transporters such as GLUT1. Inside the cell, DHA is reduced back to vitamin C by reduced glutathione (GSH) that is oxidized to glutathione disulfide (GSSG) and converted back to GSH by reduced nicotinamide adenine dinucleotide phosphate (NADPH). Depletion of GSH and NADPH results in ROS overproduction that may damage biomolecules and kill cancer cells. ROS-damaged DNA activates poly(ADP-ribose) polymerase (PARP) that requires NAD+. ROS can also inhibit glyceraldehyde 3-phosphate dehydrogenase (GAPDH) resulting in decreased production of pyruvate and ATP by mitochondria and finally energetic crisis and cell death [82–84].