Gambogic acid is an antagonist of anti-apoptotic Bcl-2-family proteins
| Autor: | Chung Wai Shiau, Shinichi Kitada, Dayong Zhai, Chaofang Jin, John C. Reed, Arnold C. Satterthwait |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Time Factors Xanthones Cell Apoptosis Binding Competitive Article Minor Histocompatibility Antigens chemistry.chemical_compound Mice Bcl-2-associated X protein Cell Line Tumor medicine Fluorescence Resonance Energy Transfer Cytotoxic T cell Animals Humans Caspase bcl-2-Associated X Protein Binding Sites biology Bcl-2 family Molecular biology Mitochondria medicine.anatomical_structure Oncology Biochemistry chemistry Proto-Oncogene Proteins c-bcl-2 Cell culture Cytoprotection biology.protein Gambogic acid Drug Screening Assays Antitumor Peptides Fluorescein-5-isothiocyanate BH3 Interacting Domain Death Agonist Protein |
| Popis: | The natural product gambogic acid (GA) has been reported to have cytotoxic activity against tumor cells in culture and was identified as an active compound in a cell-based high-throughput screening assay for activators of caspases, proteases involved in apoptosis. Using the antiapoptotic Bcl-2 family protein, Bfl-1, as a target for screening of a library of natural products, we identified GA as a competitive inhibitor that displaced BH3 peptides from Bfl-1 in a fluorescence polarization assay. Analysis of competition for BH3 peptide binding revealed that GA inhibits all six human Bcl-2 family proteins to various extents, with Mcl-1 and Bcl-B the most potently inhibited [concentrations required for 50% inhibition (IC50) |
| Databáze: | OpenAIRE |
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