Growth inhibition of prostate cancer xenografts by halofuginone

Zohar Gavish, Jehonathan H. Pinthus, Vivian Barak, Jacob Ramon, Arnon Nagler, Zelig Eshhar, Mark Pines

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND. Halofuginone, an inhibitor of collagen type I synthesis, is an anti-angiogenic agent. Here we evaluated the efficacy of halofuginone to inhibit prostate cancer (PC) xenografts representing various phenotypes of the disease. METHODS. An androgen-dependent (CWR22), an androgen-independent (PC3), and a neuroendocrine (WISH-PC2) PC xenograft were used. Halofuginone was given orally or injected intraperitoneally. Tumor size, collagen α(I) gene expression (in situ hybridization), collagen content (sirius red staining), angiogenesis (immunohistochemistry with factor VIII antibodies), and apoptosis/necrosis (DNA fragmentation) were evaluated. RESULTS. Halofuginone inhibited the growth of all subcutaneously implanted xenografts and of WISH-PC2 when transplanted orthotopically. The effect was dose-dependent (WISH-PC2) and accompanied by decrease in plasma PSA levels (CWR22). In all xenografts, halofuginone inhibited collagen α(I) gene expression, reduced collagen content, and endothelial cell number resulting in an increase in apoptosis/necrotsis. CONCLUSIONS. Oral administration of halofuginone slowed the progression of PC xenografts representing a broad range of phenotypes. Halofuginone may become a new modality for PC prevention.

Original languageEnglish
Pages (from-to)73-83
Number of pages11
JournalProstate
Volume51
Issue number2
DOIs
StatePublished - 1 May 2002
Externally publishedYes

Keywords

  • Collagen type I
  • Endothelial cells
  • Von Willebrand factor

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