Linked Life Data

18980244

Source:http://linkedlifedata.com/resource/pubmed/id/18980244

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-11-27
pubmed:abstractText
This study demonstrates that combined treatment with subtoxic doses of quercetin (3',3',4',5,7-pentahydroxyflavone), a flavonoid found in many fruits and vegetables, plus tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant hepatocellular carcinoma (HCC) cells. Effective induction of apoptosis by the combined treatment with quercetin and TRAIL was not blocked by overexpression of Bcl-xL, which is known to confer resistance to various chemotherapeutic agents. These results suggest that this combined treatment may provide an attractive strategy for treating resistant HCCs. While the proteolytic processing of procaspase-3 by TRAIL was partially blocked in various HCC cells treated with TRAIL alone, co-treatment with quercetin efficiently recovered TRAIL-induced caspase activation. We found that quercetin treatment of HCC cells significantly up-regulated the mRNA and protein levels of DR5, a death receptor of TRAIL, in a transcription factor Sp1-dependent manner. Furthermore, treatment with quercetin significantly decreased the protein levels of c-FLIP, an inhibitor of caspase-8, through proteasome-mediated degradation. Finally, administration of small interfering RNA against DR5 or overexpression of c-FLIPS, but not c-FLIPL, significantly attenuated quercetin-stimulated TRAIL-induced apoptosis. Collectively, these findings show that quercetin recovers TRAIL sensitivity in various HCC cells via up-regulation of DR5 and down-regulation of c-FLIPS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1097-4644
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1386-98
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Quercetin sensitizes human hepatoma cells to TRAIL-induced apoptosis via Sp1-mediated DR5 up-regulation and proteasome-mediated c-FLIPS down-regulation.
pubmed:affiliation
Department of Molecular Science & Technology, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't