| A bioactive probe of the oxidative pentose phosphate cycle: Novel strategy to reverse radioresistance in glucose deprived human colon cancer cells. | |
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MedLine Citation:
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PMID: 22926048 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jie Li; Kathleen M Ward; Donglan Zhang; Eswarkumar Dayanandam; Albert S Denittis; George C Prendergast; Iraimoudi S Ayene |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-16 |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: - ISSN: 1879-3177 ISO Abbreviation: Toxicol In Vitro Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Ltd. All rights reserved. |
Affiliation:
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Lankenau Institute for Medical Research, Lankenau Hospital, 100 Lancaster Avenue, Wynnewood, PA 19096, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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