Abstract
Paclitaxel (Taxol) and docetaxel (Taxotere) have been shown to inhibit angiogenesis at low concentrations that do not affect cancer cell proliferation. Here, we used rat aortic rings and human umbilical vein endothelial cells to evaluate the influence of their formulation vehicles Cremophor EL and polysorbate 80, as well as serum binding proteins on taxane-mediated antiangiogenesis. The data show that clinically relevant concentrations of the vehicles and binding proteins nullify the antiangiogenic activity of both taxanes. It is suggested that these agents may need to be used at much higher doses than anticipated for effective antiangiogenic chemotherapy.
MeSH terms
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Aorta, Thoracic / cytology
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Aorta, Thoracic / drug effects
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Blood Proteins / metabolism
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Cell Division / drug effects
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Chemistry, Pharmaceutical
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Docetaxel
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Drug Interactions
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Excipients / chemistry
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Excipients / pharmacology
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Glycerol / analogs & derivatives*
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Glycerol / chemistry
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Glycerol / pharmacology*
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Humans
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In Vitro Techniques
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Male
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Neovascularization, Pathologic / drug therapy*
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Paclitaxel / chemistry
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Paclitaxel / pharmacology*
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Pharmaceutical Vehicles / chemistry
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Pharmaceutical Vehicles / pharmacology
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Polysorbates / chemistry
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Polysorbates / pharmacology*
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Protein Binding
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Rats
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Rats, Sprague-Dawley
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Taxoids / chemistry
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Taxoids / pharmacology*
Substances
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Angiogenesis Inhibitors
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Blood Proteins
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Excipients
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Pharmaceutical Vehicles
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Polysorbates
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Taxoids
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Docetaxel
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cremophor EL
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Paclitaxel
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Glycerol