Document Detail


HDAC inhibitor-induced activation of NF-κB prevents apoptotic response of E1A+Ras-transformed cells to proapoptotic stimuli.
MedLine Citation:
PMID:  20692358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HDAC inhibitors (HDACIs) are capable of suppressing the cell growth of tumour cells due to the induction of apoptosis and/or cell cycle arrest. This allows of considering HDACIs as promising agents for tumour therapy. The final outcome - apoptotic cell death or cell cycle arrest - depends on the type of tumour and cellular context. In this report, we addressed the issue by analysing effects produced in E1A+Ras-transformed MEF cells by HDAC inhibitors sodium butyrate (NaB), Trichostatin A (TSA) and some others. It has been shown that the HDACIs induced cell cycle arrest in E1A+Ras-transformed cells but not apoptosis. The antiapoptotic effect of HDACIs is likely to be a result of NF-κB-dependent signaling pathway activation. HDACI-induced activation of NF-κB takes place in spite of a deregulated PI3K/Akt pathway in E1A+Ras cells, suggesting an alternative mechanism for the activation of NF-κB based on acetylation. HDACI-dependent activation of NF-κB prevents the induction of apoptosis by cytostatic agent adriamycin and serum deprivation. Accordingly, suppression of NF-κB activity in HDACI-arrested cells by the chemical inhibitor CAPE or RelA-siRNA resulted in the induction of an apoptotic programme. Thus, our findings suggest that the activation of the NF-κB pathway in HDACI-treated E1A+Ras-transformed cells blocks apoptosis and may thereby play a role in triggering the programme of cell cycle arrest and cellular senescence.
Authors:
M V Abramova; E A Zatulovskiy; S B Svetlikova; V A Pospelov
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-06
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  42     ISSN:  1878-5875     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-05     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1847-55     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Institute of Cytology, Russian Academy of Sciences, St-Petersburg, Russia. mav_2004@mail.ru
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MeSH Terms
Descriptor/Qualifier:
Adenovirus E1A Proteins / genetics,  metabolism*
Animals
Apoptosis
Blotting, Western
Butyrates / pharmacology*
Cell Cycle / genetics,  physiology
Cells, Cultured
Doxorubicin / pharmacology
Electrophoretic Mobility Shift Assay
Fibroblasts
Flow Cytometry
HCT116 Cells
HT29 Cells
Histone Deacetylase Inhibitors / pharmacology*
Humans
Immunoprecipitation
Mice
Microscopy, Fluorescence
NIH 3T3 Cells
Oncogene Protein p21(ras) / genetics,  metabolism*
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factor RelA / metabolism*
Chemical
Reg. No./Substance:
0/Adenovirus E1A Proteins; 0/Butyrates; 0/Histone Deacetylase Inhibitors; 0/RNA, Small Interfering; 0/Transcription Factor RelA; 23214-92-8/Doxorubicin; EC 3.6.5.2/Oncogene Protein p21(ras)

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


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