Growth inhibition of prostate cancer xenografts by halofuginone*† Journal Articles

abstract

• AbstractBACKGROUNDHalofuginone, 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.METHODSAn 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.RESULTSHalofuginone 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.CONCLUSIONSOral 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.

authors

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

status

• published 

publication date

• May 2002

has subject area

• 1103 Clinical Sciences (FoR)
• 1112 Oncology and Carcinogenesis (FoR)
• 1114 Paediatrics and Reproductive Medicine (FoR)
• Adenocarcinoma (MeSH)
• Administration, Oral (MeSH)
• Androgens (MeSH)
• Animals (MeSH)
• Antineoplastic Agents (MeSH)
• Apoptosis (MeSH)
• Collagen Type I (MeSH)
• DNA, Neoplasm (MeSH)
• Disease Progression (MeSH)
• Dose-Response Relationship, Drug (MeSH)
• Gene Expression Regulation, Neoplastic (MeSH)
• Humans (MeSH)
• Immunohistochemistry (MeSH)
• In Situ Hybridization (MeSH)
• Injections, Intraperitoneal (MeSH)
• Male (MeSH)
• Mice (MeSH)
• Mice, SCID (MeSH)
• Necrosis (MeSH)
• Neovascularization, Pathologic (MeSH)
• Oncology & Carcinogenesis (Science Metrix)
• Phenotype (MeSH)
• Piperidines (MeSH)
• Prostatic Neoplasms (MeSH)
• Quinazolines (MeSH)
• Quinazolinones (MeSH)

published in

• Prostate  Journal

keywords

• Adenocarcinoma
• Administration, Oral
• Androgens
• Animals
• Antineoplastic Agents
• Apoptosis
• Collagen Type I
• DNA, Neoplasm
• Disease Progression
• Dose-Response Relationship, Drug
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Injections, Intraperitoneal
• Male
• Mice
• Mice, SCID
• Necrosis
• Neovascularization, Pathologic
• Phenotype
• Piperidines
• Prostatic Neoplasms
• Quinazolines
• Quinazolinones

Digital Object Identifier (DOI)

• 10.1002/pros.10059

PubMed ID

• 11948962

start page

• 73

end page

• 83

volume

• 51

issue

• 2