Linked Life Data

17195089

Source:http://linkedlifedata.com/resource/pubmed/id/17195089

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-23
pubmed:abstractText
Interest in TNF-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic has been high since its first description. Recently, the use of histone deacetylase inhibitors (HDACi) to treat cancer has progressed from the laboratory to the clinic, and the combination of HDACi and TRAIL is very powerful in killing human tumors. Using a panel of prostate tumor cell lines (ALVA-31, DU-145, and LNCaP) with varying TRAIL sensitivity, we examined their sensitization to a recombinant adenovirus encoding TRAIL (Ad5-TRAIL) by sodium butyrate and trichostatin A. HDACi treatment increased coxsackie-adenovirus receptor (CAR) expression, resulting in increased adenoviral infection, and increased TRAIL-mediated killing. In TRAIL-resistant DU-145 cells, HDAC inhibition also decreased protein kinase casein kinase (PKCK) 2 activity, leading to caspase-2 activation. The importance of PKCK2 and caspase-2 in DU-145 sensitization was demonstrated with the PKCK-2-specific inhibitor, which enhanced Ad5-TRAIL-induced death, or the caspase-2-specific inhibitor, zVDVAD, which blocked Ad5-TRAIL-induced death. Thus, our data highlight the connection between HDAC inhibition of PKCK2 activity and tumor cell sensitivity to TRAIL-induced apoptosis. Specifically, HDAC inhibition leads to decreased PCKC2 activity, which is followed by caspase-2 activation and partial cleavage of caspase-8 that sensitizes the tumor cell to TRAIL.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1360-8185
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
561-71
pubmed:dateRevised
2011-7-1
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Histone deacetylase inhibitors enhance Ad5-TRAIL killing of TRAIL-resistant prostate tumor cells through increased caspase-2 activity.
pubmed:affiliation
Department of Urology, 3204 MERF, University of Iowa, 375 Newton Road, Iowa City, IA 52242-1089, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural