Clodronate inhibits angiogenesis in vitro and in vivo.
The effects of amino-bisphosphonate clodronate on endothelial cell functions involved in angiogenesis, namely proliferation and morphogenesis on matrigel were tested in vitro, whereas its effects on angiogenesis were studied in vivo. This was performed by using the chick embryo chorioallantoic membrane (CAM) assay. In vitro, clodronate inhibited the endothelial cell proliferation in a dose-dependent fashion, peaking at 30 microM. At the same concentration, clodronate inhibited the fibroblast growth factor-2 (FGF-2)-induced capillary-like tube formation in the morphogenesis assay on matrigel. In vivo, when tested with the CAM assay, clodronate again displayed the capability to inhibit FGF-2-induced angiogenesis. Overall, these results suggest that antiangiogenesis by clodronate can be used to treat a wide spectrum of angiogenesis-dependent diseases, including certain chronic inflammatory diseases and cancer.
Ribatti
D
D
Department of Human Anatomy and Histology, Policlinico, I-70124 Bari, Italy. ribatti@anatomia.uniba.it
Maruotti
N
N
Nico
B
B
Longo
V
V
Mangieri
D
D
Vacca
A
A
Cantatore
F P
FP
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002196:Capillaries / Q000378:metabolism; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism*; D004002:Clodronic Acid / Q000737:chemistry / Q000494:pharmacology*; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation; D007797:Laminin / Q000737:chemistry; D008858:Microscopy, Phase-Contrast; D009369:Neoplasms / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000737:chemistry
D020533:Angiogenesis Inhibitors; D050071:Bone Density Conservation Agents; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D004002:Clodronic Acid; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen