Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review

Wang, Lianwei; Fang, Dengyang; Xu, Jinming; Luo, Runlan

doi:10.1186/s12885-020-07568-9

Cited by 51 publications

(47 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These metabolites prevent bone resorption by inducing osteoclast apoptosis through the inhibition of ATP-dependent enzymes [77]. Conversely, next generation nitrogen-containing bisphosphonates (e.g., alendronate, ibandronate, pamidronate, risedronate and zoledronic acid) promote osteoclast apoptosis by inhibiting farnesyl pyrophosphate synthase (FPPS) and are considered more potent osteoclast inhibitors [78]. The administration of these agents may reduce the risk of SREs and skeletal morbidity rate.…”

Section: Bone-targeting Therapies For Breast Cancer Patients With Bone Metastasismentioning

confidence: 99%

Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Venetis

Piciotti

Sajjadi

et al. 2021

Cells

View full text Add to dashboard Cite

Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient’s survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients’ survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic.

show abstract

Section: Bone-targeting Therapies For Breast Cancer Patients With Bone Metastasismentioning

confidence: 99%

Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Venetis

Piciotti

Sajjadi

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…In this study, we attempted to create a distant metastasis model of the mouse breast cancer cell line E0771 (11)(12) in the femur using a versatile C57BL/6 mouse model. We verified the usefulness of this model using bone resorption inhibitors, have been shown to be useful in a mouse model of systemic administration (13). Our second aim was to assess whether we could confirm the efficacy of the bone resorption inhibitor, making this model useful for drug therapy in bone metastases.…”

mentioning

confidence: 77%

“…ZOL is a standard therapeutic agent for bone metastases and has been proposed to have direct or indirect antitumor effects in vivo (13). Furthermore, when administered as adjuvant therapy added on the standard therapy, ZOL has been shown to reduce bone metastasis in breast cancer patients with a high risk of bone metastases (22).…”

Section: Discussionmentioning

confidence: 99%

Development of New Mouse Breast Cancer Model of Local Bone Metastasis and Verification Using Bisphosphonates

Shoji

Tsuchie

Nagasawa

et al. 2022

In Vivo

View full text Add to dashboard Cite

Background/Aim: Local tumor injection models require complicated procedures. The purpose was to establish a simple local bone metastasis model using normal mice, and to study the usefulness of the model with bisphosphonates (BP). Materials and Methods: This study used a versatile C57BL/6 mouse model and E0771 cells. Tumor cells were injected into the right femur. Mice were divided into groups depending on the concentration of cells injected and the use of BP or not. The degree of bone destruction between the different conditions was compared using micro-computed tomography (μCT). Results: Bone destruction was confirmed in four mice in the highconcentration group at 3 weeks, and in all other mice at 4 and 6 weeks. At 6 weeks post-injection, bone destruction was significantly suppressed in the BP group (p<0.05). Conclusion: We created a breast cancer mouse model of local bone metastasis. Zoledronate showed the same usefulness as in previous models. It may be an effective model for evaluating treatments for bone metastasis. Materials and MethodsCell culture. E0771 (CH3 Biosystems LLC, NY) cells were cultured in Dulbecco's modified Eagle's medium (Sigma-Aldrich, St. Louis, MO, USA) supplemented with 10% fetal bovine serum (Mediatech, Manassas, VA, USA) and 100 μg/ml kanamycin sulfate (Meiji Seika Pharma, Tokyo, Japan). These were maintained in a humidified atmosphere of 5% CO 2 in air and 37˚C (14). The cells were verified 667 This article is freely accessible online.

show abstract

“…Therefore, osteoclast is one of the core targets for the treatment of osteoporosis and other bone-remodeling-related diseases. It is well known that ZA can lead to a stronger inhibition of osteoclasts differentiation and induces the apoptosis of osteoclasts ( Wang et al, 2020 ), while the underlying mechanism of ZA in the function of osteoclasts reminds unclear.…”

Section: Introductionmentioning

confidence: 99%

Zoledronic acid promotes osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation

Qu¹,

Sun²,

Wang³

et al. 2021

PeerJ

View full text Add to dashboard Cite

Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ) is a severe complication of the long-term administration of BPs. The development of BRONJ is associated with the cell death of osteoclasts, but the underlying mechanism remains unclear. In the current study, the role of Zoledronic acid (ZA), a kind of bisphosphonates, in suppressing the growth of osteoclasts was investigated and its underlying mechanism was explored. The role of ZA in regulating osteoclasts function was evaluated in the RANKL-induced cell model. Cell viability was assessed by cell counting kit-8 (CCK-8) assay and fluorescein diacetate (FDA)-staining. We confirmed that ZA treatment suppressed cell viability of osteoclasts. Furthermore, ZA treatment led to osteoclasts death by facilitating osteoclasts ferroptosis, as evidenced by increased Fe2+, ROS, and malonyldialdehyde (MDA) level, and decreased glutathione peroxidase 4 (GPX4) and glutathione (GSH) level. Next, the gene expression profiles of alendronate- and risedronate-treated osteoclasts were obtained from Gene Expression Omnibus (GEO) dataset, and 18 differentially expressed genes were identified using venn diagram analysis. Among these 18 genes, the expression of F-box protein 9 (FBXO9) was inhibited by ZA treatment. Knockdown of FBXO9 resulted in osteoclasts ferroptosis. More important, FBXO9 overexpression repressed the effect of ZA on regulating osteoclasts ferroptosis. Mechanistically, FBXO9 interacted with p53 and decreased the protein stability of p53. Collectively, our study showed that ZA induced osteoclast cells ferroptosis by triggering FBXO9-mediated p53 ubiquitination and degradation.

show abstract

Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review

Cited by 51 publications

References 121 publications

Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Development of New Mouse Breast Cancer Model of Local Bone Metastasis and Verification Using Bisphosphonates

Zoledronic acid promotes osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation

Contact Info

Product

Resources

About