ADH1, an N-cadherin inhibitor, evaluated in preclinical models of angiogenesis and androgen-independent prostate cancer.
The conversion from E-cadherin to N-cadherin has been observed in several human cancer types, including prostate cancer, with more homogenous expression of N-cadherin detected in high-grade prostate tumors. N-cadherin, in vitro, has been shown to promote cell mobility, migration and invasion of several cancer cell lines, indicating the possibility of N-cadherin as a molecular target of cancer therapy. Herein, we examined the potential of an N-cadherin inhibitor, ADH1, in reducing tumor angiogenesis ex vivo and delaying tumor progression in vivo. Our data demonstrate that ADH1, at the dosages evaluated, does not display either antiangiogenic activity in a rat aortic ring assay or antitumor potential in a PC3 subcutaneous xenograft tumor model. We detected cytotoxic activity in human umbilical vein endothelial cells, PC3, and Tsu-Pr1 cells, when ADH1 exposure was evaluated at 500 micromol/l or above.
Li
Haiqing
H
Molecular Pharmacology Section, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Price
Douglas K
DK
Figg
William D
WD
D000728:Androgens / Q000502:physiology*; D020533:Angiogenesis Inhibitors; D000818:Animals; D000970:Antineoplastic Agents; D001013:Aorta, Thoracic / Q000187:drug effects; D015153:Blotting, Western; D015820:Cadherins / Q000037:antagonists & inhibitors*; D042783:Endothelial Cells / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D051178:alpha Catenin / Q000378:metabolism
C518575:ADH-1 pepide; D000728:Androgens; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015820:Cadherins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D051178:alpha Catenin