Gavish, Z., Institute of Animal Science, The Volcani Center, P.O. Box 6, Bet Dagan, Israel
Pinthus, J.H., Department of Immunology, Weizmann Institute of Science, Rehovot, Israel, Department of Urology, Sheba Medical Center, Tel Hashomer, Israel
Barak, V., Immunology Laboratory for Tumor Diagnosis, Hadassah University Hospital, Jerusalem, Israel
Ramon, J., Department of Urology, Sheba Medical Center, Tel Hashomer, Israel
Nagler, A., Department of Bone Marrow Transplantation, Sheba Medical Center, Tel Hashomer, Israel
Eshhar, Z., Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Pines, M., Institute of Animal Science, The Volcani Center, P.O. Box 6, Bet Dagan, Israel

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. © 2002 Wiley-Liss, Inc.