Abstract
In the course of studies to discover natural products with anti-angiogenic properties, two cyclic octapeptides, octaminomycins A (1) and B (2), were isolated from the cultures of Streptomyces sp. RK85-270. Octaminomycins suppressed the vascular endothelial growth factor (VEGF)-induced proliferation, adhesion, tube formation, migration, and invasion of HUVECs. Anti-angiogenic activity was futher confirmed in vivo by the chicken chorioallantoic membrane assay. We also identified that 1 and 2 inhibited the phosphorylation of VEGF receptor 2, AKT, and ERK1/2 and the expression and activities of MMP-2 and MMP-9. These results suggest that 1 and 2 may serve as potential scaffolds for the development of therapeutic agents to angiogenesis-dependent diseases.
Keywords:
HUVEC; Octaminomycin; VEGF; anti-angiogenesis; secondary metabolites.
MeSH terms
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology*
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Cell Adhesion / drug effects
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Cells, Cultured
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Depsipeptides / chemistry
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Depsipeptides / pharmacology*
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Human Umbilical Vein Endothelial Cells / drug effects*
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Humans
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Matrix Metalloproteinases / genetics
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Matrix Metalloproteinases / metabolism
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Structure
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-akt / metabolism
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Receptors, Vascular Endothelial Growth Factor / metabolism
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Signal Transduction / drug effects
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Vascular Endothelial Growth Factor A / adverse effects
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Angiogenesis Inhibitors
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Depsipeptides
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Vascular Endothelial Growth Factor A
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octaminomycin A
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octaminomycin B
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Receptors, Vascular Endothelial Growth Factor
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases
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Matrix Metalloproteinases