אסיף מאגר המחקר החקלאי

Halofuginone: A potent inhibitor of critical steps in angiogenesis progression

Year:

2000

Source of publication :

Authors :

Volume :

14

Co-Authors:

Elkin, M., Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem 91120, Israel
Miao, H.-Q., Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem 91120, Israel
Nagler, A., Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem 91120, Israel
Aingorn, E., Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem 91120, Israel
Reich, R., Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem 91120, Israel
Hemo, I., Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem 91120, Israel
Dou, H.-L., Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem 91120, Israel
Pines, M., Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem 91120, Israel
Vlodavsky, I., Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem 91120, Israel

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Abstract:

We have previously demonstrated that halofuginone, a low molecular weight quinazolinone alkaloid, is a potent inhibitor of collagen cd (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 anglogenic 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.

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