Document Detail

A bioactive probe of the oxidative pentose phosphate cycle: novel strategy to reverse radioresistance in glucose deprived human colon cancer cells.
MedLine Citation:
PMID:  22926048     Owner:  NLM     Status:  MEDLINE    
The specific effects of glucose deprivation on oxidative pentose phosphate cycle (OPPC) function, thiol homeostasis, protein function and cell survival remain unclear due to lack of a glucose-sensitive chemical probe. Using p53 wild type and mutant human colon cells, we determined the effects of hydroxyethyl disulfide (HEDS) on NADPH, GSH, GSSG, total glutathione, total non-protein and protein thiol levels, the function of the DNA repair protein Ku, and the susceptibility to radiation-induced free radicals under normal glucose or glucose-deprived conditions. HEDS is rapidly detoxified in normal glucose but triggered a p53-independent metabolic stress in glucose depleted state that caused loss of NADPH, protein and non-protein thiol homeostasis and Ku function, and enhanced sensitivity of both p53 wild type and mutant cells to radiation induced oxidative stress. Additionally, high concentration of HEDS alone induced cell death in p53 wild type cells without significant effect on p53 mutant cells. HEDS offers a useful tool to gain insights into how glucose metabolism affects OPPC dependent stress-induced cellular functions and injury, including in tumor cells, where our findings imply a novel therapeutic approach to target glucose deprived tumor. Our work introduces a novel probe to address cancer metabolism and ischemic pathology.
Jie Li; Kathleen M Ward; Donglan Zhang; Eswarkumar Dayanandam; Albert S Denittis; George C Prendergast; Iraimoudi S Ayene
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-16
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  27     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2012-12-03     Completed Date:  2013-09-17     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  367-77     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Cesium Radioisotopes
Colonic Neoplasms
DNA Helicases / metabolism
Disulfides / pharmacology*
Ethanol / analogs & derivatives*,  pharmacology
Gamma Rays
Glucose / deficiency*
Glutathione / metabolism
Glutathione Disulfide / metabolism
HCT116 Cells
HT29 Cells
NADP / metabolism
Oxidative Stress
Pentose Phosphate Pathway / drug effects*,  physiology
Sulfhydryl Compounds / metabolism
Grant Support
Reg. No./Substance:
0/Cesium Radioisotopes; 0/Disulfides; 0/Sulfhydryl Compounds; 0/XRCC5 protein, human; 1892-29-1/2-hydroxyethyl disulfide; 3K9958V90M/Ethanol; 53-59-8/NADP; EC 3.6.4.-/DNA Helicases; GAN16C9B8O/Glutathione; IY9XDZ35W2/Glucose; ULW86O013H/Glutathione Disulfide

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

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