Figure 3.

Immune evasion of ROS through antioxidant defense in cancer survival. (A) H₂O₂ generated in the matrix can oxidize biomolecules including proteins, lipid membrane, and DNA-generating alkoxy radical by Fenton reaction. H₂O₂ generated can be converted to HO₂ by catalase, glutathione peroxidase. Glutathione exists in reduced form as GSH in the enzyme glutathione peroxidase and gets oxidized (GSSG) in the process of reduction of H₂O₂. Oxidized glutathione (GSSG) is reduced by glutathione reductase, which obtains its equivalents NADPH from HMP shunt. (B) Nrf2-ARE pathway activation takes place when cell is subjected to oxidative stress. In the cytoplasm, Nrf2 is constitutively bound to Keap1 form in the form of dimer—Nrf2-Keap1. During oxidative stress, Nrf2 is released from Keap1, hence allowing the transcriptional factor Nrf2 to translocate to the nucleus. Nrf2 in MAF family proteins binds with ARE-regulated genes. This activates antioxidant enzymes, pro-inflammatory response, and cell survival. ARE indicates antioxidant responsive element; HMP, hexose monophosphate; ROS, reactive oxygen species.