Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-10-18
pubmed:abstractText
NO-NSAIDs are promising anticancer drugs, comprising an NSAID, an NO-releasing moiety, and a spacer linking them. Although the effect of NO-NSAIDs on a wide variety of signaling and other cellular mechanisms has been deciphered, a key question remains unanswered, that being the role of NO to the overall biological effect of these agents. It has been shown that NO can directly modify sulfhydryl residues of proteins through S-nitrosylation and induce apoptosis. We studied 3 NO-NSAIDs having a different NSAID, spacer, and NO-releasing moiety. In vitro: aspirin, NO-ASA, naproxen, and NO-naproxen inhibited HT-29 human colon cancer cell growth, the IC(50)s being >5000, 192±6, 2800±210 and 95±5?M at 24h, respectively. NO-Aspirin and NO-naproxen reduced NF-?B protein levels, and activated caspase-3 enzyme in a dose- and time-dependent manner. Based on the biotin switch assay, NO-ASA and NO-naproxen S-nitrosylated NF-?B p65 in a time-dependent manner. Pretreatment of the cells with carboxy-PTIO, abrogated the S-nitrosylation of NF-?B p65. In vivo: rats treated with NO-ASA, NONO-ASA, and NO-naproxen showed S-nitrosylation of NF-?B p65 in the stomach tissue, increases in plasma TNF-?, and reductions in mucosal PGE(2) levels. These data provide a mechanistic role for NO and a rational for the chemopreventive effects of NO-NSAIDs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents..., http://linkedlifedata.com/resource/pubmed/chemical/Aspirin, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3, http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone, http://linkedlifedata.com/resource/pubmed/chemical/N-acetyl-S-(alpha-methyl-4-(2-methyl..., http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Naproxen, http://linkedlifedata.com/resource/pubmed/chemical/Nitrates, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors, http://linkedlifedata.com/resource/pubmed/chemical/S-Nitrosothiols, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/naproxen-n-butyl nitrate, http://linkedlifedata.com/resource/pubmed/chemical/nitroxy-butyl-acetylsalicylic acid
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1872-7980
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
298
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
204-11
pubmed:meshHeading
pubmed-meshheading:20674154-Animals, pubmed-meshheading:20674154-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:20674154-Aspirin, pubmed-meshheading:20674154-Blotting, Western, pubmed-meshheading:20674154-Caspase 3, pubmed-meshheading:20674154-Cell Proliferation, pubmed-meshheading:20674154-Colonic Neoplasms, pubmed-meshheading:20674154-Dinoprostone, pubmed-meshheading:20674154-Dose-Response Relationship, Drug, pubmed-meshheading:20674154-Gastric Mucosa, pubmed-meshheading:20674154-HT29 Cells, pubmed-meshheading:20674154-Humans, pubmed-meshheading:20674154-Male, pubmed-meshheading:20674154-NF-kappa B, pubmed-meshheading:20674154-Naproxen, pubmed-meshheading:20674154-Nitrates, pubmed-meshheading:20674154-Nitric Oxide, pubmed-meshheading:20674154-Nitric Oxide Donors, pubmed-meshheading:20674154-Rats, pubmed-meshheading:20674154-Rats, Wistar, pubmed-meshheading:20674154-S-Nitrosothiols, pubmed-meshheading:20674154-Signal Transduction, pubmed-meshheading:20674154-Stomach, pubmed-meshheading:20674154-Transcription Factor RelA, pubmed-meshheading:20674154-Tumor Necrosis Factor-alpha
pubmed:year
2010
pubmed:articleTitle
NO-releasing NSAIDs suppress NF-?B signaling in vitro and in vivo through S-nitrosylation.
pubmed:affiliation
Department of Physiology and Pharmacology, City University of New York Medical School, NY 10031, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural