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Thioredoxin reductase: An emerging pharmacologic target for radiosensitization of cancer
- Source :
- Translational Oncology, Vol 17, Iss, Pp 101341-(2022), Translational Oncology
- Publication Year :
- 2022
- Publisher :
- Elsevier, 2022.
-
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.<br />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.<br />Graphical abstract Image, graphical abstract
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 19365233
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Translational Oncology
- Accession number :
- edsair.doi.dedup.....9aaf62bdf3583fc4416746fca6cdfb01