Document Detail


Thioredoxin reductase 1 deficiency enhances selenite toxicity in cancer cells via a thioredoxin-independent mechanism.
MedLine Citation:
PMID:  22594686     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Selenium is an essential trace element in mammals, but is toxic at high levels. It is best known for its cancer prevention activity, but cancer cells are more sensitive to selenite toxicity than normal cells. Since selenite treatment leads to oxidative stress, and the Trx (thioredoxin) system is a major antioxidative system, we examined the interplay between TR1 (Trx reductase 1) and Trx1 deficiencies and selenite toxicity in DT cells, a malignant mouse cell line, and the corresponding parental NIH 3T3 cells. TR1-deficient cells were far more sensitive to selenite toxicity than Trx1-deficient or control cells. In contrast, this effect was not seen in cells treated with hydrogen peroxide, suggesting that the increased sensitivity of TR1 deficiency to selenite was not due to oxidative stress caused by this compound. Further analyses revealed that only TR1-deficient cells manifested strongly enhanced production and secretion of glutathione, which was associated with increased sensitivity of the cells to selenite. The results suggest a new role for TR1 in cancer that is independent of Trx reduction and compensated for by the glutathione system. The results also suggest that the enhanced selenite toxicity of cancer cells and simultaneous inhibition of TR1 can provide a new avenue for cancer therapy.
Authors:
Ryuta Tobe; Min-Hyuk Yoo; Noelia Fradejas; Bradley A Carlson; Soledad Calvo; Vadim N Gladyshev; Dolph L Hatfield
Related Documents :
2714406 - A close relationship between microvilli and metabolic cooperation deficiency in embryon...
20395446 - Podocalyxin ebp50 ezrin molecular complex enhances the metastatic potential of renal ce...
20501806 - Oncogenic functions of secreted frizzled-related protein 2 in human renal cancer.
22609376 - Eriodictyol protects against h(2)o(2)-induced neuron-like pc12 cell death through activ...
23316476 - Crosstalk between bcl-2 family and ras family small gtpases: potential cell fate regula...
6707106 - Arrest states in a set of mutants of rat 3y1 cells temperature-sensitive for entering s...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  445     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-13     Completed Date:  2012-09-26     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  423-30     Citation Subset:  IM    
Affiliation:
Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Anticarcinogenic Agents / pharmacology
Base Sequence
Cell Line, Tumor
Gene Knockdown Techniques
Glutathione / metabolism
Hydrogen Peroxide / pharmacology
Mice
NIH 3T3 Cells
Neoplasms, Experimental / drug therapy*,  metabolism*
Oxidative Stress / drug effects
RNA, Small Interfering / metabolism
Sodium Selenite / pharmacology*
Thioredoxin Reductase 1 / antagonists & inhibitors,  deficiency*,  genetics,  metabolism
Thioredoxins / metabolism
Grant Support
ID/Acronym/Agency:
CA080946/CA/NCI NIH HHS; GM065204/GM/NIGMS NIH HHS; R01 CA080946/CA/NCI NIH HHS; R01 GM065204/GM/NIGMS NIH HHS; R37 GM065204/GM/NIGMS NIH HHS; ZIA BC010889-05/BC/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/RNA, Small Interfering; 10102-18-8/Sodium Selenite; 52500-60-4/Thioredoxins; 70-18-8/Glutathione; 7722-84-1/Hydrogen Peroxide; EC 1.8.1.9/Thioredoxin Reductase 1; EC 1.8.1.9/Txnrd1 protein, mouse
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis.
Next Document:  The effect of an oxygenating agent on chlorhexidine-induced extrinsic tooth staining: a systematic r...