Nrf2 signaling pathway in cisplatin chemotherapy: Potential involvement in organ protection and chemoresistance

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a vital transcription factor and its induction is of significant importance for protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) stimulate Nrf2 signaling, enhancing the activity of antioxidant enzymes such as catalase, superoxide dismutase and Abbreviations: Nrf2, nuclear factor erythroid 2-related factor 2; ARE, antioxidant response element; ROS, reactive oxygen species; HO-1, heme oxygenase-1; NQO1, NAD(p)H quinone oxidoreductase 1; SLC7A11, solute carrier family 7 membrane 11; GPX, glutathione peroxidase; CP, cisplatin; CAT, catalase; SOD, superoxide dismutase; PI3K, phosphoinositide 3-kinase; Akt, protein kinase-B; TR1, thioredoxin reductase 1; 5-FU, 5-fluorouracil; PAQR4, Progestion and AdipoQ Receptor 4; lncRNA, long non-coding RNA; UCA1, urothelial cancer associated 1; NER, nucleotide excision repair; BER, base excision repair; GLUT3, glucose transporter 3; GSK-3b, glycogen synthase kinase-3 beta; Aila, Ailanthone; miRNA, microRNA; Hsp90, heat shock protein 90; EGFR, epidermal growth factor receptor; UA, ursolic acid; ER, endoplasmic reticulum; CHOP, CCAAT-enhancer-binding protein homologous protein; HIF-1a, hypoxia inducible factor-1a; GPx4, glutathione peroxidase 4; STAT3, signal transducer and activator of transcription 3; Scrib, scribble; PD-L1, programmed death-ligand 1; PAR1, pseudoautosomal region 1; ATP, ABC-binding cassette; TMD, transmembrane domain; NBD, nucleotide-binding domain; MAPK, mitogen-activated protein kinase; MKP-1, MAPK phosphatase 1; Cul3, cullin3; ATGs, autophagy-related genes; siRNA, small interfering RNA; NES, NRF2 nuclear export signal; JNK, c-Jun N-terminal kinase; ncRNAs, non-coding RNAs; ceRNA, competing endogenous RNA; TUG1, taurine upregulated gene 1; 3/-UTR, 3/-untranslated region; MDA, malondialdehyde; PIC, piceatannol; Res, resveratrol; BBB, blood-brain barrier; EGCG, epigallocatechin gallate; TMP, tetramethylpyrazine; ALS, amyotrophic lateral sclerosis; AKI, acute kidney injury; mTOR, mammalian target of rapamycin; SIRTs, sirtuins; LC-3, light chain-3.

Nrf2, Cisplatin