Linked Life Data

20022690

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

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pubmed-article:20022690pubmed:abstractTextNuclear 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.lld:pubmed
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pubmed-article:20022690pubmed:authorpubmed-author:ChoiYung...lld:pubmed
pubmed-article:20022690pubmed:authorpubmed-author:KimGi-YoungGYlld:pubmed
pubmed-article:20022690pubmed:authorpubmed-author:MoonDong-OhDOlld:pubmed
pubmed-article:20022690pubmed:authorpubmed-author:ParkSung...lld:pubmed
pubmed-article:20022690pubmed:authorpubmed-author:KimMun-OckMOlld:pubmed
pubmed-article:20022690pubmed:authorpubmed-author:KangSang-Hyuc...lld:pubmed
pubmed-article:20022690pubmed:copyrightInfoCopyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.lld:pubmed
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pubmed-article:20022690pubmed:articleTitleHA14-1 sensitizes TNF-alpha-induced apoptosis via inhibition of the NF-kappaB signaling pathway: involvement of reactive oxygen species and JNK.lld:pubmed
pubmed-article:20022690pubmed:affiliationLaboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, Republic of Korea.lld:pubmed
pubmed-article:20022690pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:20022690pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed