Linked Life Data

20022690

Source:http://linkedlifedata.com/resource/pubmed/id/20022690

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-4-13
pubmed:abstractText
Nuclear factor-kappa B (NF-kappaB) activation by tumor necrosis factor-alpha (TNF-alpha) attenuates the TNF-alpha-induced apoptosis pathway. Thus, blockage of NF-kappaB activity may improve the anti-cancer activity of TNF-alpha. HA14-1 induces apoptosis in various human cancer cells, and the molecular mechanisms of this action remain to be fully characterized. The present study evaluated the involvement of NF-kappaB, reactive oxygen species (ROS), and c-Jun N-terminal kinase (JNK) in the effects of HA14-1 by examining the sensitization effect on TNF-alpha-induced apoptosis in human leukemia cells. Such sensitization is closely associated with the inhibitory effect of HA14-1 on TNF-alpha-mediated NF-kappaB activation. HA14-1 suppressed NF-kappaB activation through inhibition of phosphorylation and degradation of IkappaBalpha. This inhibition was correlated with suppression of NF-kappaB-dependent gene products (c-myc, cyclin D1, cox-2, and IAP-1). Additionally, the present findings provide evidence of a critical role of ROS accumulation induced by HA14-1 in TNF-alpha-induced apoptosis. Moreover, HA14-1 also markedly sustained TNF-alpha-mediated JNK activation. A specific JNK inhibitor abolished the sensitization effect of HA14-1 on TNF-alpha-induced apoptosis. Taken together, these results indicate that ROS and JNK represent important signals in HA14-1 sensitization in TNF-alpha-induced apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1872-7980
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
292
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
111-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
HA14-1 sensitizes TNF-alpha-induced apoptosis via inhibition of the NF-kappaB signaling pathway: involvement of reactive oxygen species and JNK.
pubmed:affiliation
Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't