Cited by 854Bone health and treatmentsAngiogenesis and VEGF in CancerBone Metabolism and Diseases

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Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid.

Wood, Jeanette, Bonjean, Karine, Ruetz, Stephan, Bellahcène, Akeila, Devy, Laetitia, Foidart, Jean Michel, Castronovo, Vincent, Green, Jonathan R.·2002·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1124/jpet.102.035295

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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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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)
DOI: 10.1124/jpet.102.035295
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid.

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