Document Detail


Interferon-gamma enhances radiation-induced cell death via downregulation of Chk1.
MedLine Citation:
PMID:  22825336     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interferon-gamma (IFNγ) is a cytokine with roles in immune responses as well as in tumor control. Interferon is often used in cancer treatment together with other therapies. Here we report a novel approach to enhancement of cancer cell killing by combined treatment of IFNγ with ionizing radiation. We found that IFNγ treatment alone in HeLa cells induced phosphorylation of Chk1 in a time- and dose-dependent manner, and resulted in cell arrest. Moreover IFNγ treatment was correlated with attenuation of Chk1 as the treatment shortened protein half-life of Chk1. As Chk1 is an essential cell cycle regulator for viability after DNA damage, attenuation of Chk1 by IFNγ pre-treatment in HeLa cells resulted in increased cell death following ionizing radiation about 2-folds than ionizing radiation treatment alone whereas IFNγ treatment alone had little effect on cell death. X-linked inhibitor of apoptosis-associated factor 1 (XAF1), an IFN-induced gene, seems to partly regulate IFNγ-induced Chk1 destabilization and radiation sensitivity because transient depletion of XAF1 by siRNA prevented IFNγ-induced Chk1 attenuation and partly protected cells from IFNγ-enhanced radiation cell killing. Therefore the results provide a novel rationale to combine IFNγ pretreatment and DNA-damaging anti-cancer drugs such as ionizing radiation to enhance cancer cell killing.
Authors:
Kwang Seok Kim; Kyu Jin Choi; Sangwoo Bae
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-24
Journal Detail:
Title:  Cancer biology & therapy     Volume:  13     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-12     Completed Date:  2013-04-11     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1018-25     Citation Subset:  IM    
Affiliation:
Divisions of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle / drug effects,  radiation effects
Cell Death / drug effects,  radiation effects
Cell Line, Tumor
Cell Survival
Combined Modality Therapy
Down-Regulation / drug effects
HeLa Cells
Humans
Interferon-gamma / pharmacology*
Intracellular Signaling Peptides and Proteins / deficiency,  genetics,  metabolism
Lung Neoplasms / drug therapy*,  enzymology,  genetics,  radiotherapy*
Neoplasm Proteins / deficiency,  genetics,  metabolism
Phosphorylation / drug effects
Protein Kinases / genetics,  metabolism*
RNA, Small Interfering / administration & dosage,  genetics
Transfection
Chemical
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Neoplasm Proteins; 0/RNA, Small Interfering; 0/XAF1 protein, human; 82115-62-6/Interferon-gamma; EC 2.7.-/Protein Kinases; EC 2.7.11.1/Checkpoint kinase 1
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