Diphenylureas for Treatment of Prostate Cancer
Abstract
We have synthesized and characterized a unique group of diphenylureas that are much more potent than suramin or its sulfonated analogues as inhibitors of cell growth, migration and matrix metalloproteinase activity (MMP-2 and MMP-9) in human microvascular endothelial and human prostate cancer cell lines (PC3, LNCaP.FGC and DU145) in vitro. Toxicity studies in mice indicate no significant toxicity by the diphenylureas and a half-life 10-fold less than suramin. However, the diphenylureas do not bind the heparin-like growth factors. These results suggest that the diphenylureas could be potent inhibitors of prostate cancer in vivo that could reduce morbidity in man. The experiments described in this proposal were the first in vivo test of the ability of a unique group of diphenylureas to inhibit the growth and metastasis in human androgen dependent (LNCaP) and androgen independent (PC3) prostate tumor xenografts in nude mice. We proposed that the diphenylureas were potent inhibitors of tumorigenesis, angiogenesis and metastasis in human prostate cancer growth. Furthermore, the antineoplastic activity of the diphenylureas was thought not to have its effect by inhibition of growth factors binding as has been demonstrated for suramin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2002
- Accession Number
- ADB282207
Entities
People
- Delwood C. Collins
Organizations
- University of Kentucky