Document Detail

TSA-induced cell death in prostate cancer cell lines is caspase-2 dependent and involves the PIDDosome.
MedLine Citation:
PMID:  17110788     Owner:  NLM     Status:  MEDLINE    
The histone deacetylase inhibitor Trichostatin A (TSA) has previously been found to induce caspase activity in the human prostate cancer cell lines DU145 and LNCaP. TSA treatment resulted in the release of cytochrome c and Smac/DIABLO from mitochondria in DU145, and activation of caspase-9 in both cell lines. We concluded that TSA mediated its effect via the mitochondrial pathway. The aim of the current study was to determine how TSA initiated the caspase cascade. The results revealed that caspase-2 plays an important role in TSA-induced apoptosis. Inhibition of caspase-2 by siRNA or expression of caspase-2dn substantially decreased caspase activity after TSA treatment in both cell lines, siRNA caspase-2 also inhibited TSA-induced cell death. Caspase-2 acts upstream of caspase-8 and -9 and mediates mitochondrial cytochrome c release. Coimmunoprecipitation experiments show that caspase-2 formed protein complexes with RADD/RAIDD and PIDD. Together, these data indicate that caspase-2 initiates caspase cascade after TSA treatment and involves the formation of the PIDDosome.
Agshin F Taghiyev; Natalya V Guseva; Rebecca A Glover; Oskar W Rokhlin; Michael B Cohen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-09-09
Journal Detail:
Title:  Cancer biology & therapy     Volume:  5     ISSN:  1538-4047     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-11-20     Completed Date:  2007-04-20     Revised Date:  2011-10-14    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1199-205     Citation Subset:  IM    
Department of Pathology, The University of Iowa, Iowa City, Iowa 52242-1087, USA.
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MeSH Terms
CRADD Signaling Adaptor Protein / metabolism
Carrier Proteins / genetics,  metabolism*
Caspase 2 / genetics,  metabolism*
Caspase 8 / metabolism
Caspase 9 / metabolism
Cell Death / drug effects
Cell Line, Tumor
Cytochromes c / metabolism
Enzyme Activation / drug effects
Histone Deacetylase Inhibitors
Hydroxamic Acids / pharmacology*
Mitochondria / drug effects,  metabolism
Prostatic Neoplasms / drug therapy*,  genetics,  metabolism,  pathology
RNA, Small Interfering / genetics
Grant Support
Reg. No./Substance:
0/CRADD Signaling Adaptor Protein; 0/CRADD protein, human; 0/Carrier Proteins; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/PIDD protein, human; 0/RNA, Small Interfering; 58880-19-6/trichostatin A; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 2; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9

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

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