Molecular-Targeted Antitumor Agents. 19. Furospongolide from a Marine Lendenfeldia sp. Sponge Inhibits Hypoxia-Inducible Factor-1 Activation in Breast Tumor Cells
| Autor: | Mika B. Jekabsons, Yu-Dong Zhou, Dale G. Nagle, J. Brian Morgan, Yang Liu, Rui Liu, Shui-Chun Mao |
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| Rok vydání: | 2008 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Organic Chemistry Pharmaceutical Science Biological activity Biology In vitro Analytical Chemistry Cell biology Vascular endothelial growth factor Vascular endothelial growth factor A chemistry.chemical_compound Complementary and alternative medicine Mechanism of action chemistry Biochemistry Cell culture Oxidoreductase Drug Discovery medicine Molecular Medicine Cytotoxic T cell medicine.symptom |
| Zdroj: | Journal of Natural Products. 71:1854-1860 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | A natural product chemistry-based approach was employed to discover small-molecule inhibitors of the important tumor-selective molecular target hypoxia-inducible factor-1 (HIF-1). Bioassay-guided isolation of an active lipid extract of a Saipan collection of the marine sponge Lendenfeldia sp. afforded the terpene-derived furanolipid furospongolide as the primary inhibitor of hypoxia-induced HIF-1 activation (IC50 2.9 μM, T47D breast tumor cells). The active component of the extract also contained one new cytotoxic scalarane sesterterpene and two previously reported scalaranes. Furospongolide blocked the induction of the downstream HIF-1 target secreted vascular endothelial growth factor (VEGF) and was shown to suppress HIF-1 activation by inhibiting the hypoxic induction of HIF-1α protein. Mechanistic studies indicate that furospongolide inhibits HIF-1 activity primarily by suppressing tumor cell respiration via the blockade of NADH-ubiquinone oxidoreductase (complex I)-mediated mitochondrial electron tra... |
| Databáze: | OpenAIRE |
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