אסיף מאגר המחקר החקלאי

Inhibition of bladder carcinoma angiogenesis, stromal support, and tumor growth by halofuginone

Year:

1999

Source of publication :

Authors :

Volume :

59

Co-Authors:

Elkin, M., Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel, Department of Biological Chemistry, Silberman Institute of Life Sciences, Hebrew University, Jerusalem 91904, Israel
Ariel, I., Department of Pathology, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel
Miao, H.-Q., Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel, Department of Surgical Research, Children's Hospital, Boston, MA 02115, United States
Nagler, A., Department of Bone Marrow Transplant, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel
Pines, M., Institute of Animal Science, Volcany Center, Bet Dagan 50250, Israel
De-Groot, N., Department of Biological Chemistry, Silberman Institute of Life Sciences, Hebrew University, Jerusalem 91904, Israel
Hochberg, A., Department of Biological Chemistry, Silberman Institute of Life Sciences, Hebrew University, Jerusalem 91904, Israel
Vlodavsky, I., Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel, Department of Oncology, Hadassah Hospital, P. O. Box 12000, Jerusalem 91120, Israel

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Abstract:

We have previously demonstrated that halofuginone, a widely used alkaloid coccidiostat, is a potent inhibitor of collagen α1(I) and matrix metalloproteinase 2 gene expression. Halofuginone also suppresses extracellular matrix deposition and cell proliferation. We investigated the effect of halofuginone on transplantable and chemically induced mouse bladder carcinoma. In both systems, oral administration of halofuginone resulted in a profound anticancerous effect, even when the treatment was initiated at advanced stages of tumor development. Although halofuginone failed to prevent proliferative preneoplastic alterations in the bladder epithelium, it inhibited further progression of the chemically induced tumor into a malignant invasive stage. Histological examination and in situ analysis of the tumor tissue revealed a marked decrease in blood vessel density and in both collagen α1(I) and H19 gene expression. H19 is regarded as an early marker of bladder carcinoma. The antiangiogenic effect of halofuginone was also demonstrated by inhibition of microvessel formation in vitro. We attribute the profound antitumoral effect of halofuginone to its combined inhibition of the tumor stromal support, vascularization, invasiveness, and cell proliferation.

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