Document Detail


Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells.
MedLine Citation:
PMID:  18497575     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In recent years, cellular redox environment gained significant attention as a critical regulator of cellular responses to oxidative stress. Cellular redox environment is a balance between production of reactive oxygen species and their removal by antioxidant enzymes. We investigated the hypothesis that mitochondrial antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells. Vector-control and manganese superoxide dismutase (MnSOD) overexpressing human pancreatic cancer cells were irradiated and assayed for cell survival and activation of the G(2)-checkpoint pathway. Increased MnSOD activity significantly increased cell survival following irradiation with 6 Gy of gamma-radiation (p < 0.05). The MnSOD overexpressing irradiated cells also revealed 3-4 folds increase in the percentage of G(2) cells compared to irradiated vector-control. Furthermore, MnSOD overexpressing irradiated cells exhibited increased loss of phosphorylated histone H2AX protein levels. The radiation-induced increase in cyclin B1 protein levels in irradiated vector-control cells was suppressed in irradiated MnSOD overexpressing cells. Mitochondria-targeted catalase overexpression increased the survival of irradiated cells. These results support the hypothesis that mitochondrial antioxidant enzyme activity and mitochondria-generated reactive oxygen species-signaling (superoxide and hydrogen peroxide) could regulate radiation-induced G(2) checkpoint activation and radioresistance in human pancreatic cancer cells.
Authors:
Carolyn J Fisher; Prabhat C Goswami
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-13
Journal Detail:
Title:  Cancer biology & therapy     Volume:  7     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-09-04     Completed Date:  2008-12-31     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1271-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / metabolism*
Catalase / metabolism
Cell Survival / radiation effects
Cyclin B / metabolism
Cyclin B1
Dose-Response Relationship, Radiation
Gene Expression Regulation, Enzymologic / radiation effects
Gene Expression Regulation, Neoplastic / radiation effects
Humans
Mitochondria / enzymology*,  genetics,  metabolism
Models, Biological
Pancreatic Neoplasms / enzymology*,  genetics,  metabolism
Radiation Tolerance / genetics,  physiology*
Reactive Oxygen Species / metabolism
Superoxide Dismutase / metabolism
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA078586-0651/CA/NCI NIH HHS; CA111365/CA/NCI NIH HHS; R01 CA111365/CA/NCI NIH HHS; R01 CA111365-01A2/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/CCNB1 protein, human; 0/Cyclin B; 0/Cyclin B1; 0/Reactive Oxygen Species; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase
Comments/Corrections

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