The Alternative Medicine Pawpaw and Its Acetogenin Constituents Suppress Tumor Angiogenesis via the HIF-1/VEGF Pathway
| Autor: | Yang Liu, Fakhri Mahdi, Veena Coothankandaswamy, Yu-Dong Zhou, J. Brian Morgan, Shui-Chun Mao, Dale G. Nagle, Mika B. Jekabsons |
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| Rok vydání: | 2010 |
| Předmět: |
Complementary Therapies
Asimina Acetogenins Angiogenesis Annonacin Neovascularization Physiologic Pharmaceutical Science Pharmacology Biology Article Analytical Chemistry Neovascularization Inhibitory Concentration 50 chemistry.chemical_compound Drug Discovery medicine Humans Cytotoxicity Glucose Transporter Type 1 Plants Medicinal Molecular Structure Vascular Endothelial Growth Factors Organic Chemistry Antineoplastic Agents Phytogenic In vitro Complementary and alternative medicine chemistry Mechanism of action Cell culture Acetogenin Molecular Medicine Hypoxia-Inducible Factor 1 Drug Screening Assays Antitumor medicine.symptom |
| Zdroj: | Journal of Natural Products. 73:956-961 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | Products that contain twig extracts of pawpaw (Asimina triloba, Annonaceae) are widely consumed anticancer alternative medicines. Pawpaw crude extract (CE) and purified acetogenins inhibited hypoxia-inducible factor-1 (HIF-1)-mediated hypoxic signaling pathways in tumor cells. In T47D cells, pawpaw CE and the acetogenins 10-hydroxyglaucanetin (1), annonacin (2), and annonacin A (3) inhibited hypoxia-induced HIF-1 activation with IC50 values of 0.02 μg/mL, 12 nM, 13 nM, and 31 nM, respectively. This inhibition correlates with the suppression of the hypoxic induction of HIF-1 target genes VEGF and GLUT-1. The induction of secreted VEGF protein represents a key event in hypoxia-induced tumor angiogenesis. Both the extract and the purified acetogenins blocked the angiogenesis-stimulating activity of hypoxic T47D cells in vitro. Pawpaw extract and acetogenins inhibited HIF-1 activation by blocking the hypoxic induction of nuclear HIF-1α protein. The inhibition of HIF-1 activation was associated with the suppression of mitochondrial respiration at complex I. Thus, the inhibition of HIF-1 activation and hypoxic tumor angiogenesis constitutes a novel mechanism of action for these anticancer alternative medicines. |
| Databáze: | OpenAIRE |
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