RT Journal Article
SR Electronic
T1 Novel Antiangiogenic Effects of the Bisphosphonate Compound Zoledronic Acid
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1055
OP 1061
DO 10.1124/jpet.102.035295
VO 302
IS 3
A1 Jeanette Wood
A1 Karine Bonjean
A1 Stephan Ruetz
A1 Akeila Bellahcène
A1 Laetitia Devy
A1 Jean Michel Foidart
A1 Vincent Castronovo
A1 Jonathan R. Green
YR 2002
UL http://jpet.aspetjournals.org/content/302/3/1055.abstract
AB Bisphosphonate drugs inhibit osteoclastic bone resorption and are widely used to treat skeletal complications in patients with tumor-induced osteolysis. We now show that zoledronic acid, a new generation bisphosphonate with a heterocyclic imidazole substituent, is also a potent inhibitor of angiogenesis. In vitro, zoledronic acid inhibits proliferation of human endothelial cells stimulated with fetal calf serum, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (IC50 values 4.1, 4.2, and 6.9 μM, respectively), and modulates endothelial cell adhesion and migration. In cultured aortic rings and in the chicken egg chorioallantoic membrane assay, zoledronic acid reduces vessel sprouting. When administered systemically to mice, zoledronic acid potently inhibits the angiogenesis induced by subcutaneous implants impregnated with bFGF [ED50, 3 μg/kg (7.5 nmol/kg) s.c.]. These findings indicate that zoledronic acid has marked antiangiogenic properties that could augment its efficacy in the treatment of malignant bone disease and extend its potential clinical use to other diseases with an angiogenic component. The American Society for Pharmacology and Experimental Therapeutics