NADPH Oxidases: Insights into Selected Functions and Mechanisms of Action in Cancer and Stem Cells

Figure 2

Endogenous sources and consequences of ROS overproduction. Overproduction of superoxide anion and H₂O₂ by NOX (NOX and Duox), cytochrome c oxidase, or xanthine oxidase (XO) and the subsequent increased level of hydroxyl radical (generated through the Fenton or Haber-Weiss reaction) are leading to lipids, proteins, and nucleic acid oxidation and, in consequence, to genomic instability, mutations, and carcinogenesis. Upon this conditions, cell survival or death is dependent on the activation of either ASK-1 or PI3K: high level of ROS tends to activate the ASK-1/JNK pathway leading to cell death, while lower or transient ROS production may result in the activation of PI3K kinase (accompanied by ASK-1/JNK inhibition) and NF-κB-mediated survival.