Abstract
Therapeutic doses of zoledronic acid markedly inhibit in vitro proliferation, chemotaxis, and capillarogenesis of bone marrow endothelial cells of patients with multiple myeloma. Zoledronic acid also induces a sizeable reduction of angiogenesis in the in vivo chorioallantoic membrane assay. These effects are partly sustained by gene and protein inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in an autocrine loop. Mevastatin, a specific inhibitor of the mevalonate pathway, reverts the zoledronic acid antiangiogenic effect, indicating that the drug halts this pathway. Our results provide evidence of a direct antiangiogenic activity of zoledronic acid on multiple myeloma patient-derived endothelial cells due to at least four different mechanisms identified either in vitro or in vivo. Tentatively, we suggest that the zoledronic acid antitumoral activity in multiple myeloma is also sustained by antiangiogenesis, which would partly account for its therapeutic efficacy in multiple myeloma.
| Original language | English |
|---|---|
| Pages (from-to) | 3256-3262 |
| Number of pages | 7 |
| Journal | Molecular Cancer Therapeutics |
| Volume | 6 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2007 |
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ASJC Scopus subject areas
- Oncology
- Drug Discovery
- Pharmacology
Cite this
Zoledronic acid affects over-angiogenic phenotype of endothelial cells in patients with multiple myeloma. / Scavelli, Claudio; Di Pietro, Giulia; Cirulli, Teresa; Coluccia, Mauro; Boccarelli, Angela; Giannini, Teresa; Mangialardi, Giuseppe; Bertieri, Raffaello; Coluccia, Addolorata Maria Luce; Ribatti, Domenico; Dammacco, Franco; Vacca, Angelo.
In: Molecular Cancer Therapeutics, Vol. 6, No. 12, 01.12.2007, p. 3256-3262.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Zoledronic acid affects over-angiogenic phenotype of endothelial cells in patients with multiple myeloma
AU - Scavelli, Claudio
AU - Di Pietro, Giulia
AU - Cirulli, Teresa
AU - Coluccia, Mauro
AU - Boccarelli, Angela
AU - Giannini, Teresa
AU - Mangialardi, Giuseppe
AU - Bertieri, Raffaello
AU - Coluccia, Addolorata Maria Luce
AU - Ribatti, Domenico
AU - Dammacco, Franco
AU - Vacca, Angelo
PY - 2007/12/1
Y1 - 2007/12/1
N2 - Therapeutic doses of zoledronic acid markedly inhibit in vitro proliferation, chemotaxis, and capillarogenesis of bone marrow endothelial cells of patients with multiple myeloma. Zoledronic acid also induces a sizeable reduction of angiogenesis in the in vivo chorioallantoic membrane assay. These effects are partly sustained by gene and protein inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in an autocrine loop. Mevastatin, a specific inhibitor of the mevalonate pathway, reverts the zoledronic acid antiangiogenic effect, indicating that the drug halts this pathway. Our results provide evidence of a direct antiangiogenic activity of zoledronic acid on multiple myeloma patient-derived endothelial cells due to at least four different mechanisms identified either in vitro or in vivo. Tentatively, we suggest that the zoledronic acid antitumoral activity in multiple myeloma is also sustained by antiangiogenesis, which would partly account for its therapeutic efficacy in multiple myeloma.
AB - Therapeutic doses of zoledronic acid markedly inhibit in vitro proliferation, chemotaxis, and capillarogenesis of bone marrow endothelial cells of patients with multiple myeloma. Zoledronic acid also induces a sizeable reduction of angiogenesis in the in vivo chorioallantoic membrane assay. These effects are partly sustained by gene and protein inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in an autocrine loop. Mevastatin, a specific inhibitor of the mevalonate pathway, reverts the zoledronic acid antiangiogenic effect, indicating that the drug halts this pathway. Our results provide evidence of a direct antiangiogenic activity of zoledronic acid on multiple myeloma patient-derived endothelial cells due to at least four different mechanisms identified either in vitro or in vivo. Tentatively, we suggest that the zoledronic acid antitumoral activity in multiple myeloma is also sustained by antiangiogenesis, which would partly account for its therapeutic efficacy in multiple myeloma.
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UR - http://www.scopus.com/inward/citedby.url?scp=37549004818&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-07-0311
DO - 10.1158/1535-7163.MCT-07-0311
M3 - Article
C2 - 18089719
AN - SCOPUS:37549004818
VL - 6
SP - 3256
EP - 3262
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
SN - 1535-7163
IS - 12
ER -