Inhibition of Neovascularization and Tumor Growth, and Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I Synthesis

Rinat Abramovitch, Hagit Dafni, Michal Neeman, Arnon Nagler, Mark Pines

Research output: Contribution to journalArticlepeer-review

Abstract

Halofuginone, an inhibitor of collagen α1(l) 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, and these spheroids showed no collagen α1(l) 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 μg every 48 hours) administration of halofuginone. In these mice, treatment was associated with a dose-dependent reduction in collagen α1(l) 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, and 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.

Original languageEnglish
Pages (from-to)321-329
Number of pages9
JournalNeoplasia
Volume1
Issue number4
DOIs
StatePublished - Oct 1999
Externally publishedYes

Keywords

  • C6 glioma
  • Collagen type I
  • Halofuginone
  • MRI

Fingerprint

Dive into the research topics of 'Inhibition of Neovascularization and Tumor Growth, and Facilitation of Wound Repair, by Halofuginone, an Inhibitor of Collagen Type I Synthesis'. Together they form a unique fingerprint.

Cite this