Fig. 1. Redox signaling and oxidative stress in normal and cancer cells.

The major signaling cascades induced by growth factor-stimulated ROS are highlighted on the left. The same pathways influence the cell cycle and affect the activity of transcription factors and genes that play roles in the cellular response to the hypoxic microenvironment. ROS also induce lipid peroxidation with commensurate electron leakage in mitochondria and the release of Ca²⁺ from intracellular stores. The main consequences of oxidative stress in cancer cells are illustrated on the right. Moderately elevated ROS induce oncogenes and inhibit tumor suppressor genes that, in turn, increase ROS levels. Ca²⁺ release induces PKC, while the expression of genes involved in the formation of new blood vessels and in the establishment of a boosted antioxidant system is enhanced. ROS also activate HDACs and have a dual effect on DNMTs with important outcomes for the expression of oncogenes and tumor suppressor genes. Oxidized bases trigger mutations and engage DNA repair enzymes.