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Growth inhibition of prostate cancer xenografts by halofuginone * †
Author(s) -
Gavish Zohar,
Pinthus Jehonathan H.,
Barak Vivian,
Ramon Jacob,
Nagler Ar,
Eshhar Zelig,
Pines Mark
Publication year - 2002
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10059
Subject(s) - medicine , angiogenesis , cancer research , prostate cancer , pathology , apoptosis , prostate , cancer , biology , biochemistry
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 α1(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 α1(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. Prostate 51: 73–83, 2002. © 2002 Wiley‐Liss, Inc.