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rdf:type |
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lifeskim:mentions |
umls-concept:C0002028,
umls-concept:C0012780,
umls-concept:C0037083,
umls-concept:C0127400,
umls-concept:C0215848,
umls-concept:C0242184,
umls-concept:C0431085,
umls-concept:C1458155,
umls-concept:C1566172,
umls-concept:C1710082,
umls-concept:C1822686,
umls-concept:C2348110,
umls-concept:C2348977
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pubmed:issue |
12
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pubmed:dateCreated |
2004-12-28
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pubmed:abstractText |
The degree of tumor hypoxia correlates with advanced disease stages and treatment resistance. The transcription factor hypoxia-inducible factor-1 (HIF-1) promotes tumor cell adaptation and survival under hypoxic conditions. Therefore, specific HIF-1 inhibitors represent an important new class of potential tumor-selective therapeutic agents. A T47D human breast tumor cell-based reporter assay was used to examine extracts of plants and marine organisms for inhibitors of HIF-1 activation. Bioassay-guided fractionation of the lipid extract of the red alga Laurencia intricata yielded a structurally novel diterpene, laurenditerpenol (1). The structure of 1 was determined spectroscopically. The relative configurations of the substituents of each ring system were assigned on the basis of NOESY correlations. The absolute configuration of position C-1 was determined by the modified Mosher ester procedure (directly in NMR tubes). Compound 1 potently inhibited hypoxia-activated HIF-1 (IC50: 0.4 microM) and hypoxia-induced VEGF (a potent angiogenic factor) in T47D cells. Compound 1 selectively inhibits HIF-1 activation by hypoxia but not iron chelator-induced activation. Further, 1 suppresses tumor cell survival under hypoxic conditions without affecting normoxic cell growth. Compound 1 inhibits HIF-1 by blocking the induction of the oxygen-regulated HIF-1alpha protein. Mitochondrial respiration studies revealed that 1 suppresses oxygen consumption.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-10582706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-10606224,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-10715308,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-10910041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-10924166,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-10945599,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-11100117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-11156418,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-11181778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-11208848,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-11226230,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-11292861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-11292862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-11374951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-11479209,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-12154035,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-12350147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-12761491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-12778165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-13130303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-14510540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-14510602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-14526383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-14671307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-15165135,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-3335022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-8260699,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-8534867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-9000051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-9223322,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-9291439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-9393757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15620241-9751731
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0163-3864
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2002-7
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pubmed:dateRevised |
2011-4-28
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pubmed:meshHeading |
pubmed-meshheading:15620241-Anoxia,
pubmed-meshheading:15620241-Antineoplastic Agents,
pubmed-meshheading:15620241-Breast Neoplasms,
pubmed-meshheading:15620241-DNA-Binding Proteins,
pubmed-meshheading:15620241-Diterpenes,
pubmed-meshheading:15620241-Dose-Response Relationship, Drug,
pubmed-meshheading:15620241-Humans,
pubmed-meshheading:15620241-Hypoxia-Inducible Factor 1,
pubmed-meshheading:15620241-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:15620241-Mitochondria,
pubmed-meshheading:15620241-Molecular Structure,
pubmed-meshheading:15620241-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:15620241-Nuclear Proteins,
pubmed-meshheading:15620241-Rhodophyta,
pubmed-meshheading:15620241-Stereoisomerism,
pubmed-meshheading:15620241-Transcription Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Laurenditerpenol, a new diterpene from the tropical marine alga Laurenciaintricata that potently inhibits HIF-1 mediated hypoxic signaling in breast tumor cells.
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pubmed:affiliation |
Department of Pharmacognosy, National Center for Natural Products Research, and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677-1848, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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