Linked Life Data

21319187

Source:http://linkedlifedata.com/resource/pubmed/id/21319187

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-4
pubmed:abstractText
The synthetic retinoid fenretinide is one of the most promising clinically tested retinoids. Previously, we have shown that fenretinide induces apoptosis of Huh7 cells, but HepG2 cells are relatively resistant to fenretinide-induced apoptosis. This study examines the interactive role of fenretinide and histone deacetylase inhibitors (HDACi) in inducing apoptosis of human hepatocellular carcinoma (HCC) cells and the underlying mechanism. Trichostatin A and scriptaid can either enhance fenretinide-induced apoptosis in the fenretinide sensitive HCC cells (Huh7 and Hep3B) or sensitize the fenretinide resistant cells (HepG2) to become sensitive to the apoptotic effect of fenretinide in a cancer cell-specific manner. The sensitivity of cells to fenretinide-induced apoptosis was not associated with reactive oxygen species production nor with antioxidant gene expression. However, the level of retinoic acid receptor ? (RAR?) and Nur77 (NR4A1) was important for inducing apoptosis. Upon fenretinide and HDACi treatment, the expression of RAR? and Nur77 were induced and colocalized in the cytosol. The induction of Nur77 protein level, but not the messenger RNA level, was RAR?-dependent. In addition, RAR? interacted with Nur77. Nur77 was essential for fenretinide-induced and HDACi-induced apoptosis of Huh7 cells. Induction of the expression, the interaction, and the nuclear export of RAR? and Nur77 mediate fenretinide-induced and HDACi-induced apoptosis. CONCLUSION: Our findings suggest that targeting Nur77 and RAR? simultaneously provides an effective way to induce HCC cell death.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants, http://linkedlifedata.com/resource/pubmed/chemical/Fenretinide, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxylamines, http://linkedlifedata.com/resource/pubmed/chemical/NR4A1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 4..., http://linkedlifedata.com/resource/pubmed/chemical/Quinolines, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid, http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor beta, http://linkedlifedata.com/resource/pubmed/chemical/scriptaid, http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1527-3350
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 American Association for the Study of Liver Diseases.
pubmed:issnType
Electronic
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
865-74
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Enrichment of Nur77 mediated by retinoic acid receptor ? leads to apoptosis of human hepatocellular carcinoma cells induced by fenretinide and histone deacetylase inhibitors.
pubmed:affiliation
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural