Halofuginone: a potent inhibitor of critical steps in angiogenesis progression
| Autor: | Michael Elkin, Mark Pines, Israel Vlodavsky, Itzhak Hemo, Hua-Quan Miao, Arnon Nagler, Reuven Reich, Hong-Liang Dou, Elena Aingorn |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Angiogenesis
Basic fibroblast growth factor Neovascularization Physiologic Angiogenesis Inhibitors Matrix metalloproteinase Biochemistry Neovascularization Extracellular matrix chemistry.chemical_compound Piperidines Genetics medicine Animals Molecular Biology Aorta Quinazolinones Dose-Response Relationship Drug Halofuginone Capillaries Rats Endothelial stem cell chemistry Tumor progression Quinazolines Cancer research Matrix Metalloproteinase 2 Cattle Fibroblast Growth Factor 2 Endothelium Vascular medicine.symptom Biotechnology medicine.drug |
| Zdroj: | The FASEB Journal. 14:2477-2485 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.00-0292com |
| Popis: | We have previously demonstrated that halofuginone, a low molecular weight quinazolinone alkaloid, is a potent inhibitor of collagen alpha1(I) and matrix metalloproteinase 2 (MMP-2) gene expression. Halofuginone also effectively suppresses tumor progression and metastasis in mice. These results together with the well-documented role of extracellular matrix (ECM) components and matrix degrading enzymes in formation of new blood vessels led us to investigate the effect of halofuginone on the angiogenic process. In a variety of experimental system, representing sequential events in the angiogenic cascade, halofuginone treatment resulted in profound inhibitory effect. Among these are the abrogation of endothelial cell MMP-2 expression and basement membrane invasion, capillary tube formation, and vascular sprouting, as well as deposition of subendothelial ECM. The most conclusive anti-angiogenic activity of halofuginone was demonstrated in vivo (mouse corneal micropocket assay) by showing a marked inhibition of basic fibroblast growth factor (bFGF) -induced neovascularization in response to systemic administration of halofuginone, either i.p. or in the diet. The ability of halofuginone to interfere with key events in neovascularization, together with its oral bioavailability and safe use as an anti-parasitic agent, make it a promising drug for further evaluation in the treatment of a wide range of diseases associated with pathological angiogenesis. |
| Databáze: | OpenAIRE |
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