1. Thioredoxin reductase: An emerging pharmacologic target for radiosensitization of cancer
- Author
-
Raghavendra S. Patwardhan, Deepak Sharma, and Santosh K. Sandur
- Subjects
Cancer Research ,TrxR, thioredoxin reductase ,PDI, protein disulfide isomerase ,MSR, methionine sulfoxide reductase ,PMA, phorbol-12-myristic acid ,ARE, antioxidant response element ,Review ,SAPK, stress activated protein kinase ,CypD, cyclophilin D ,ROS, reactive oxygen species ,G.R., glutathione reductase ,NSCLC, non-small cell lung cancer ,HNSCC, head & neck squamous cell carcinoma ,Nrf2, nuclear factor erythroid 2 related factor 2 ,Trx, thioredoxin ,MnSOD, manganese superoxide dismutase ,Con A, concanavalin A ,Thioredoxin ,RC254-282 ,PEG, polyethylene glycol ,PTEN, Phosphatase and Tensin Homolog ,TNF, tumor necrosis factor ,Radiation ,APE1, apurinic/apyrimidinic endonuclease 1 ,N.F.-κB, nuclear factor kappa B ,Hif1α, hypoxia inducible factor 1 α ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,BSO, buthionine sulfoximine ,Ref-1, redox factor 1 ,RNR, ribonucleotide reductase ,IQ9, indolequinone 9 ,NADPH, nicotinamide adenine dinucleotide phosphate ,Thioredoxin reductase ,PRX, peroxiredoxin ,SLNB, solid lipid nanoparticles of baicalein ,Oncology ,Sec, selenocysteine ,FAD, flavine adenine dinucleotide ,IR, ionizing radiation ,LPS, lipopolysaccharide ,GNP, gold nanoparticle ,LLC, Lewis lung carcinoma ,ASK1, apoptosis signaling kinase ,Grx2, glutaredoxin 2 ,AIF, apoptosis inducing factor ,Redox homeostasis - Abstract
Highlights • Thioredoxin reductase (TrxR), a seleno enzyme, regulates cellular redox. • Several human cancers are known to overexpress TrxR. • Inhibitors of TrxR have enhanced radiation induced cytotoxicity in multiple cancers. • TrxR could be a potential target during radiotherapy of cancer patients., Novel agents are required to increase the radiosensitivity of cancer and improve the outcome of radiotherapy. Thioredoxin (Trx) and thioredoxin reductase (TrxR) reduce the oxidized cysteine thiols in several proteins, which regulate cellular redox, survival, proliferation, DNA synthesis, transcription factor activity and apoptosis. TrxR is essential for maintaining a conducive redox state for tumor growth, survival and resistance to therapy. Therefore, it is an appealing pharmacological target for the radiosensitization of tumors. Ionizing radiation (IR) is known to cause cytotoxicity through ROS, oxidative stress and DNA damage. Inhibition of thioredoxin system augments IR induced oxidative stress and potentiates cytotoxic effects. However, TrxR also regulates several critical cellular processes in normal cells. Here, we highlight the pre-clinical research and pharmacological studies to surmise possible utility of different TrxR inhibitors for radiosensitization. This review provides a succinct perspective on the role of TrxR inhibitors during the radiotherapy of cancer., Graphical abstract Image, graphical abstract
- Published
- 2022