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SirT1 regulates radiosensitivity of hepatoma cells differently under normoxia and hypoxia conditions.
MedLine Citation:
PMID:  22448750     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Intratumoral hypoxic cells are more resistant to radiotherapy for reduction in life span of DNA-damaging free radicals and augmentation of post-irradiation molecular restoration. SirT1, a member of the mammalian sirtuin family, deacetylates various transcription factors to trigger cell defense and survival in response to stresses and DNA damage. In this study, we furnished novel evidence indicating that over expression of SirT1 in hepatoma HepG2 cells allowed the cells to become much more resistant to irradiation under hypoxia condition than that under normoxia. While in contrast, when SirT1 was knocked down in both HepG2 and SK-Hep-1 cells, the radiosensitivity was increased especially under hypoxia condition. But this enhanced radiosensitivity in SirT1 deficient cells was extensively decreased by infecting cells with c-Myc siRNA. Furthermore, the expression of c-Myc protein and its acetylation were increased in the SirT1 knockdown cells and these increments under hypoxia condition were much more notable than that under normoxia. In addition, c-Myc interfere remarkably suppressed p-p53 protein expression after irradiation, especially under hypoxic conditions. The current findings indicate that SirT1 confers a higher radioresistance in hypoxic cells than that of normoxia due to the decreased levels of c-Myc protein and its acetylation and that a c-Myc-dependent radiation-induced p-p53 may be involved in, suggesting that SirT1 could be served as a novel target of radiation damage and thus as a potential strategy to advance the efficiency of radiotherapy in hepatoma entities.
Authors:
Yuexia Xie; Jianghong Zhang; Shuang Ye; Mingyuan He; Ruiping Ren; Dexiao Yuan; Chunlin Shao
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-26
Journal Detail:
Title:  Cancer science     Volume:  -     ISSN:  1349-7006     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Japanese Cancer Association.
Affiliation:
Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai, 200032, China.
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