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Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid.
Abstract
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 (IC(50) values 4.1, 4.2, and 6.9 microM, 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 [ED(50), 3 microg/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.
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“these agents have also been shown to suppress the proliferation, adhesion, migration, and survival of endothelial cells in vitro (147, 148) while inducing endothelial cell apoptosis in vivo (149).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [147]
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Metadata
- Authors
- Wood, J., Bonjean, K., Ruetz, S., Bellahcène, A., Devy, L., Foidart, J. M., Castronovo, V., & Green, J. R.
- Affiliations
- Novartis (Switzerland) (CH)
- University of Liège (BE)
- ORCID
- Bellahcène, Akeila
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 302
- Issue
- 3
- Pages
- 1055-1061
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2144860907
- Cited by
- 854
- References
- 33
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 14 · 2023: 20 · 2022: 17 · 2021: 18 · 2020: 22 · 2019: 34 · 2018: 23 · 2017: 20 · 2016: 24 · 2015: 38 · 2014: 46 · 2013: 44 · 2012: 36
- FWCI
- 14.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- zoledronic acid, bisphosphonates, antiangiogenic activity, angiogenesis inhibition, endothelial cell proliferation, basic fibroblast growth factor, vascular endothelial growth factor, endothelial cell adhesion, endothelial cell migration, tumor-induced osteolysis, malignant bone disease, chorioallantoic membrane assay
- MeSH terms
- Zoledronic Acid, Pamidronate, Cell Adhesion, Cell Cycle, Cell Movement, Cells, Cultured, Chemotaxis, Chorion, Diphosphonates, Endothelium, Vascular, Growth Substances, Humans, Imidazoles, Lymphokines, Muscle, Smooth, Vascular, Fibroblast Growth Factor 2, Endothelial Growth Factors, Apoptosis, Image Cytometry, Angiogenesis Inhibitors, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A
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