Abstract
Rapidly increasing experimental and clinical data provides evidence for the role of hypoxia inducible factor-1 (HIF-1) as a crucial mediator of tumor survival and progression. In our effort to identify inhibitors of the HIF-1 activation pathway, we screened fractions from marine invertebrates. Fractions from an extract of Petrosia (Strongylophora) strongylata potently inhibited the HIF-1 activation pathway. Strongylophorines 2, 3, and 8 isolated from the active fractions were found to be responsible for the HIF-1 inhibition with EC 50 values of 8, 13, and 6 microM, respectively.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Hypoxia
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Cell Line, Tumor
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Cell Survival / drug effects
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Diterpenes / chemistry
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Diterpenes / isolation & purification
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Diterpenes / pharmacology*
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Drug Screening Assays, Antitumor
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Genes, Reporter
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Humans
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Hypoxia-Inducible Factor 1 / antagonists & inhibitors*
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Hypoxia-Inducible Factor 1 / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
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Luciferases / genetics
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Petrosia / chemistry*
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Structure-Activity Relationship
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Transcription, Genetic
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Vascular Endothelial Growth Factor A / biosynthesis
Substances
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Antineoplastic Agents
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Diterpenes
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Hypoxia-Inducible Factor 1
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Hypoxia-Inducible Factor 1, alpha Subunit
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Vascular Endothelial Growth Factor A
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Luciferases