ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Figure 2

ROS sources and antioxidant systems. Mitochondrial respiration ETC and the membrane-bond NOX complexes are the two major ROS resources. Leakage of electrons from ETC is mediated by coenzyme Q and produces O₂^- through O₂. There are three isoforms of SODs to defend oxidation. Cu/Zn SOD (SOD1) in the cytoplasm, MnSOD (SOD2) in the mitochondria, and Cu/Zn SOD (SOD3) in the extracellular matrix can rapidly convert O₂^- to H₂O₂. NOXs catalyze the generation of O₂^- from O₂ and NADPH. H₂O₂ is converted to toxic ·OH by a metal (Fe²⁺ or Cu⁺) catalyst through the Fenton reaction. H₂O₂ can be converted into H₂O by PRXs, GPXs, and CAT. Besides, Trxs (the cytoplasmic Trx-1 and the mitochondrial Trx-2) can reduce oxidized PRXs. Trxs themselves are also reduced to TrxR by TR using NADPH as an electron donor. GPXs oxidize reduced GSH to GSSH. GSSH is reduced back to GSH by GR accompanied by an electron from NADPH. Note. ETC: electron transport chain; NOXs: NADPH oxidase; SODs: superoxide dismutases; H₂O₂: hydrogen peroxide; NADPH: nicotinamide adenine dinucleotide phosphate; ·OH: hydroxyl radicals; PRXs: peroxiredoxins; GPXs: glutathione peroxidases; CAT: catalase; Trx: thioredoxin (oxidized); Trx-R: thioredoxin (reduced); TR: thioredoxin reductase; GSH: tripeptide glutathione (reduced); GSSH: glutathione disulfide (oxidized); GR: glutathione. Green dotted lines denote H₂O₂ diffusion. Red dotted lines denote O₂^- diffusion.