Inhibition of Neovascularization and Tumor Growth, Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I Synthesis
Halofuginone, an inhibitor of collagen α1(I) gene expression was used for the treatment of subcutaneously implanted C6 glioma tumors. Halofuginone had no effect on the growth of C6 glioma spheroids in vitro, these spheroids showed no collagen α1(I) expression and no collagen synthesis. However, a s...
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doaj-806b0442913c4e178e440b199fb3ee992020-11-24T23:20:25ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80021999-10-011432132910.1038/sj.neo.7900043Inhibition of Neovascularization and Tumor Growth, Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I SynthesisRinat Abramovitch0Hagit Dafni1Michal Neeman2Amon Nagler3Mark Pines4Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem 91120Institute of Animal Science, Agricultural Research Organization, The Volcani Center, Bet Dagan 50250, Israel Halofuginone, an inhibitor of collagen α1(I) gene expression was used for the treatment of subcutaneously implanted C6 glioma tumors. Halofuginone had no effect on the growth of C6 glioma spheroids in vitro, these spheroids showed no collagen α1(I) expression and no collagen synthesis. However, a significant attenuation of tumor growth was observed in vivo, for spheroids implanted in CD-1 nude mice which were treated by oral or intraperitoneal (4 μtg every 48 hours) administration of halofuginone. In these mice, treatment was associated with a dose-dependent reduction in collagen α1(I) expression and dose- and time-dependent inhibition of angiogenesis, as measured by MRI. Moreover, halofuginone treatment was associated with improved re-epithelialization of the chronic wounds that are associated with this experimental model. Oral administration of halofuginone was effective also in intervention in tumor growth, here, too, the treatment was associated with reduced angiogenic activity and vessel regression. These results demonstrate the important role of collagen type I in tumor angiogenesis and tumor growth and implicate its role in chronic wounds. Inhibition of the expression of collagen type I provides an attractive new target for cancer therapy. http://www.sciencedirect.com/science/article/pii/S1476558699800232halofuginoneC6 gliomaCollagen type IMRI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rinat Abramovitch Hagit Dafni Michal Neeman Amon Nagler Mark Pines |
spellingShingle |
Rinat Abramovitch Hagit Dafni Michal Neeman Amon Nagler Mark Pines Inhibition of Neovascularization and Tumor Growth, Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I Synthesis Neoplasia: An International Journal for Oncology Research halofuginone C6 glioma Collagen type I MRI |
author_facet |
Rinat Abramovitch Hagit Dafni Michal Neeman Amon Nagler Mark Pines |
author_sort |
Rinat Abramovitch |
title |
Inhibition of Neovascularization and Tumor Growth, Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I Synthesis |
title_short |
Inhibition of Neovascularization and Tumor Growth, Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I Synthesis |
title_full |
Inhibition of Neovascularization and Tumor Growth, Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I Synthesis |
title_fullStr |
Inhibition of Neovascularization and Tumor Growth, Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I Synthesis |
title_full_unstemmed |
Inhibition of Neovascularization and Tumor Growth, Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I Synthesis |
title_sort |
inhibition of neovascularization and tumor growth, facilitation of wound repair, by halofuginone, an inhibitor of collagen type i synthesis |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
1999-10-01 |
description |
Halofuginone, an inhibitor of collagen α1(I) gene expression was used for the treatment of subcutaneously implanted C6 glioma tumors. Halofuginone had no effect on the growth of C6 glioma spheroids in vitro, these spheroids showed no collagen α1(I) expression and no collagen synthesis. However, a significant attenuation of tumor growth was observed in vivo, for spheroids implanted in CD-1 nude mice which were treated by oral or intraperitoneal (4 μtg every 48 hours) administration of halofuginone. In these mice, treatment was associated with a dose-dependent reduction in collagen α1(I) expression and dose- and time-dependent inhibition of angiogenesis, as measured by MRI. Moreover, halofuginone treatment was associated with improved re-epithelialization of the chronic wounds that are associated with this experimental model. Oral administration of halofuginone was effective also in intervention in tumor growth, here, too, the treatment was associated with reduced angiogenic activity and vessel regression. These results demonstrate the important role of collagen type I in tumor angiogenesis and tumor growth and implicate its role in chronic wounds. Inhibition of the expression of collagen type I provides an attractive new target for cancer therapy.
|
topic |
halofuginone C6 glioma Collagen type I MRI |
url |
http://www.sciencedirect.com/science/article/pii/S1476558699800232 |
work_keys_str_mv |
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