The thioredoxin system: a key target in tumour and endothelial cells.
Thioredoxin is a redox-sensitive molecule that has pleiotropic cellular effects, such as the control of proliferation, redox states and apoptosis, and is often upregulated in malignancy. The system controls the activation of a number of transcription factors through sulphydryl transfer and, through its activity on hypoxia inducible factor 1alpha, it is able to regulate vascular endothelial growth factor levels and hence angiogenesis. The thioredoxin protein has been shown to be upregulated in hypoxic regions of certain tumours, suggesting that inhibitors could potentially exhibit enhanced hypoxic toxicity and/or indirect anti-angiogenic effects. Evidence of this is becoming apparent in the literature. The current report reviews the thioredoxin system as an anticancer drug target and focuses upon two recent compounds, PMX464 and PX12, which reportedly inhibit this important pathway.
Mukherjee
A
A
Department of Clinical Oncology, Nottingham University Hospitals, City Hospital Campus, Hucknall Road, Nottingham NG5 1PB, UK.
Martin
S G
SG
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000494:pharmacology; D002417:Cattle; D003512:Cyclohexanones / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D009369:Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D013879:Thioredoxins / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C515226:AW 464; D020533:Angiogenesis Inhibitors; D052160:Benzothiazoles; D003512:Cyclohexanones; D004220:Disulfides; D006873:Hydroquinones; D051793:Hypoxia-Inducible Factor 1; D007093:Imidazoles; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D013879:Thioredoxins; C412893:1-methylpropyl-2-imidazolyl disulfide