A novel non-containing-nitrogen bisphosphonate inhibits both in vitro and in vivo angiogenesis

Hamma-Kourbali, Yamina; Benedetto, Mélanie Di; Ledoux, Dominique; Oudar, Olivier; Leroux, Yves; Lecouvey, Marc; Kraemer, Michel

doi:10.1016/j.bbrc.2003.09.083

Cited by 62 publications

(46 citation statements)

References 29 publications

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“…Several authors have suggested that a compromised blood supply secondary to BPs is the initiating event in the development of the ONJ lesion (7). While a significant number of studies have shown that BPs inhibit angiogenesis, the overwhelming majority of these investigations were performed in vitro (most commonly using human umbilical vein endothelial cells) or in vivo in animal models (13)(14)(15)(16)(17)(18). Apoptosis or programmed cell death is a process where living cells participate in a cascade of events that ends with the cell dying.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Oral Mucosal Cell Wound Healing by Bisphosphonates

Landesberg

Cozin

Cremers

et al. 2008

Journal of Oral and Maxillofacial Surgery

278

161

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Bisphosphonates are a widely used class of drugs that have been proven to be extremely useful in the prevention and treatment of osteoporosis, hypercalcemia of malignancy, and bone metastases associated with multiple myeloma, breast cancer, and other solid tumors. In the past several years there have been numerous reports describing the occurrence of Osteonecrosis of the Jaws (ONJ) associated with these drugs. In the great majority of cases this condition develops after surgical manipulation of the oral tissues. The natural history and pathophysiology of ONJ however, remains unknown at the present time. Furthermore, whether the ONJ lesion initiates in the oral mucosa or derives from the underlying bone has not been determined. In this report we describe the effect of pamidronate, a second generation bisphosphonate, on oral mucosal cells. Our results show that bisphosphonate pre-treatment of oral mucosal cells inhibits proliferation and wound healing at clinically relevant doses and that this inhibition is not due to cellular apoptosis.

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Section: Discussionmentioning

confidence: 99%

“…Another hypothesis is that ONJ is a result of the inhibition of angiogenesis by the bisphosphonates. While several reports have shown that bisphosphonates decrease angiogenesis, almost all of these studies have only been performed in vitro and in transgenic animal models (13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Oral Mucosal Cell Wound Healing by Bisphosphonates

Landesberg

Cozin

Cremers

et al. 2008

Journal of Oral and Maxillofacial Surgery

278

161

View full text Add to dashboard Cite

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“…We were thus led to consider a much different agent, zoledronic acid (ZA; Zometa), a nitrogen-containing (amino-) bisphosphonate (N-BP) that is FDA approved to reduce skeletal complications of bone metastasis in patients with multiple myeloma and several solid tumor types with minimal side effects (24,25). Recent studies in cell culture and xenotransplant tumor models have variously suggested that ZA and other BPs have antiangiogenic and MMP-inhibitory activity (26)(27)(28)(29)(30)(31). These data led us to test ZA on cervical neoplasias in HPV/E 2 mice.…”

Section: Figurementioning

confidence: 99%

An amino-bisphosphonate targets MMP-9–expressing macrophages and angiogenesis to impair cervical carcinogenesis

2004

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A mouse model involving the human papillomavirus type-16 oncogenes develops cervical cancers by lesional stages analogous to those in humans. In this study the angiogenic phenotype was characterized, revealing intense angiogenesis in high-grade cervical intraepithelial neoplasias (CIN-3) and carcinomas. MMP-9, a proangiogenic protease implicated in mobilization of VEGF, appeared in the stroma concomitant with the angiogenic switch, expressed by infiltrating macrophages, similar to what has been observed in humans. Preclinical trials sought to target MMP-9 and angiogenesis with a prototypical MMP inhibitor and with a bisphosphonate, zoledronic acid (ZA), revealing both to be antiangiogenic, producing effects comparable to a Mmp9 gene KO in impairing angiogenic switching, progression of premalignant lesions, and tumor growth. ZA therapy increased neoplastic epithelial and endothelial cell apoptosis without affecting hyperproliferation, indicating that ZA was not antimitotic. The analyses implicated cellular and molecular targets of ZA's actions: ZA suppressed MMP-9 expression by infiltrating macrophages and inhibited metalloprotease activity, reducing association of VEGF with its receptor on angiogenic endothelial cells. Given its track record in clinical use with limited toxicity, ZA holds promise as an "unconventional" MMP-9 inhibitor for antiangiogenic therapy of cervical cancer and potentially for additional cancers and other diseases where MMP-9 expression by infiltrating macrophages is evident.

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“…Heterocycle in the side chain is implicated in the induction of cell apoptosis by preventing the prenylation of signalling proteins such as Ras or Rho (Luckman et al, 1998). Inhibition of Ras processing using non bromo-containing BP7033 is also reached (Hamma-kourbali et al, 2003). Also, the addition of phenyl function in the side chain of BPs rendered the catalytic pocket of geranyl and/or farnesyl synthase enzymes of the mevalonate pathway more accessible (Mao et al, 2006;Steeg et al, 2006).…”

Section: Bisphosphonate Esterificationsmentioning

confidence: 99%

New Experimental Therapies Targetting Breast Cancer Cell

Melanie¹

2011

Breast Cancer - Current and Alternative Therapeutic Modalities

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A novel non-containing-nitrogen bisphosphonate inhibits both in vitro and in vivo angiogenesis

Cited by 62 publications

References 29 publications

Inhibition of Oral Mucosal Cell Wound Healing by Bisphosphonates

Inhibition of Oral Mucosal Cell Wound Healing by Bisphosphonates

An amino-bisphosphonate targets MMP-9–expressing macrophages and angiogenesis to impair cervical carcinogenesis

New Experimental Therapies Targetting Breast Cancer Cell

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