Asparagine Endopeptidase Inhibitor Can Prevent Breast Cancer Bone Metastasis by Attenuating Osteoclast Differentiation and Function

2021 ◽  
Author(s):  
Junsong Chen ◽  
Wenke Xu ◽  
Xia Chen ◽  
Kaiyuan Song ◽  
Lin-Tai Da ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Osteoclast Differentiation ◽  
Breast Cancer Bone Metastasis ◽  
And Function

scholarly journals Combination of AZD3463 and DZNep Prevents Bone Metastasis of Breast Cancer by Suppressing Akt Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenxin He ◽  
Xiankun Cao ◽  
Kewei Rong ◽  
Xiaojun Chen ◽  
Shuai Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Osteoclast Differentiation ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Anti Cancer ◽  
Breast Cancer Bone Metastasis ◽  
Cancer Agent

Osteolysis resulting from osteoclast overactivation is one of the severe complications of breast cancer metastasis to the bone. Previous studies reported that the anti-cancer agent DZNep induces cancer cell apoptosis by activating Akt signaling. However, the effect of DZNep on breast cancer bone metastasis is unknown. We previously found that DZNep enhances osteoclast differentiation by activating Akt. Therefore, we explored the use of the anti-cancer agent AZD3463 (an Akt inhibitor) along with DZNep, as AZD3463 can act as an anti-cancer agent and can also potentially ameliorate bone erosion. We evaluated osteoclast and breast cancer cell phenotypes and Akt signaling in vitro by treating cells with DZNep and AZD3463. Furthermore, we developed a breast cancer bone metastasis animal model in mouse tibiae to further determine their combined effects in vivo. Treatment of osteoclast precursor cells with DZNep alone increased osteoclast differentiation, bone resorption, and expression of osteoclast-specific genes. These effects were ameliorated by AZD3463. The combination of DZNep and AZD3463 inhibited breast cancer cell proliferation, colony formation, migration, and invasion. Finally, intraperitoneal injection of DZNep and AZD3463 ameliorated tumor progression and protected against bone loss. In summary, DZNep combined with AZD3463 prevented skeletal complications and inhibited breast cancer progression by suppressing Akt signaling.

Increased COX2 expression enhances tumor-induced osteoclastic lesions in breast cancer bone metastasis

2008 ◽  
Vol 68 (S 01) ◽  
Author(s):  
C Schem ◽  
DO Bauerschlag ◽  
J Weimer ◽  
M Zhang ◽  
W Jonat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Breast Cancer Bone Metastasis ◽  
Cox2 Expression

Biological and Toxicological Evaluation of N-(4methyl-phenyl)-4-methylphthalimide on Bone Cancer in Mice

2019 ◽  
Vol 19 (5) ◽  
pp. 667-676
Author(s):  
José R. Santin ◽  
Gislaine F. da Silva ◽  
Maria V.D. Pastor ◽  
Milena F. Broering ◽  
Roberta Nunes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
In Silico ◽  
Bone Matrix ◽  
Micronucleus Assay ◽  
Repeated Treatment ◽  
Toxicological Evaluation ◽  
Toxicological Analysis ◽  
Breast Cancer Bone Metastasis

Background: It was recently demonstrated that the phthalimide N-(4-methyl-phenyl)-4- methylphthalimide (MPMPH-1) has important effects against acute and chronic pain in mice, with a mechanism of action correlated to adenylyl cyclase inhibition. Furthermore, it was also demonstrated that phthalimide derivatives presented antiproliferative and anti-tumor effects. Considering the literature data, the present study evaluated the effects of MPMPH-1 on breast cancer bone metastasis and correlated painful symptom, and provided additional toxicological information about the compound and its possible metabolites. Methods: In silico toxicological analysis was supported by in vitro and in vivo experiments to demonstrate the anti-tumor and anti-hypersensitivity effects of the compound. Results: The data obtained with the in silico toxicological analysis demonstrated that MPMPH-1 has mutagenic potential, with a low to moderate level of confidence. The mutagenicity potential was in vivo confirmed by micronucleus assay. MPMPH-1 treatments in the breast cancer bone metastasis model were able to prevent the osteoclastic resorption of bone matrix. Regarding cartilage, degradation was considerably reduced within the zoledronic acid group, while in MPMPH-1, chondrocyte multiplication was observed in random areas, suggesting bone regeneration. Additionally, the repeated treatment of mice with MPMPH-1 (10 mg/kg, i.p.), once a day for up to 36 days, significantly reduces the hypersensitivity in animals with breast cancer bone metastasis. Conclusion: Together, the data herein obtained show that MPMPH-1 is relatively safe, and significantly control the cancer growth, allied to the reduction in bone reabsorption and stimulation of bone and cartilage regeneration. MPMPH-1 effects may be linked, at least in part, to the ability of the compound to interfere with adenylylcyclase pathway activation.

The effects of hydroxyapatite nanoparticles on breast cancer bone metastasis in 3-D scaffolds

Bone ◽  
2011 ◽  
Vol 48 ◽  
pp. S253 ◽  
Author(s):  
D.D. Lin ◽  
S.P. Pathi ◽  
C. Fischbach-Teschl ◽  
L.A. Estroff
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Hydroxyapatite Nanoparticles ◽  
Breast Cancer Bone Metastasis

scholarly journals Expression of Osteoprotegerin and RANK Ligand in Breast Cancer Bone Metastasis

2003 ◽  
Vol 18 (4) ◽  
pp. 541 ◽  
Author(s):  
Hye Rim Park ◽  
Soo Kee Min ◽  
Hyun Deuk Cho ◽  
Duck Hwan Kim ◽  
Hyung Sik Shin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Rank Ligand ◽  
Breast Cancer Bone Metastasis

Development of a Novel 3D Bioprinted In Vitro Nano Bone Model for Breast Cancer Bone Metastasis Study

2014 ◽  
Vol 1724 ◽  
Author(s):  
Benjamin Holmes ◽  
Wei Zhu ◽  
Lijie Grace Zhang
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Metastatic Breast ◽  
Bone Microstructure ◽  
Bone Model ◽  
Skeletal Complications ◽  
3D Printed ◽  
Breast Cancer Bone Metastasis

ABSTRACTBreast cancer (BrCa) is the second commonest cause of cancer-related deaths in women. The metastatic breast cancer exhibits a high affinity to bone, leading to debilitating skeletal complications associated with significant morbidity and poor prognosis. Traditional in vitro and in vivo BrCa bone metastasis models contain many inherent limitations with regards to controllability, reproducibility, and flexibility of design. Thus, the objective of this research is to use a 3D bioprinting system and nanomaterials to recreate a biomimetic and tunable bone model suitable for the effective simulation and study of metastatic BrCa invading and colonizing a bone environment. For this purpose, we designed and 3D printed a series of scaffolds, comprised of a bone microstructure and nano hydroxyapatites (nHA, inorganic nano components in bone). The size and geometry of the bone microstructure was varied with 250 and 150 µm pores, in repeating square and hexagon patterns, for a total of four different pore geometries. 3D bioprinted scaffolds were subsequently conjugated with nHA, using an acetylation chemical functionalization process and then characterized by scanning electron microscope (SEM). SEM imaging showed that our designed microfeatures were printable with the predesigned resolutions described above. Imaging further confirmed that acetylation effectively attached nHA to the surface of scaffolds and induced a nanoroughness. Metastatic BrCa cell 4 h adhesion and 1, 3 and 5 day proliferation were investigated in the bone model in vitro. The cell adhesion and proliferation results showed that all scaffolds are cytocompatible for BrCa cell growth; in particular the nHA scaffolds with small hexagonal pores had the highest cell density. Given this data, it can be stipulated that our 3D printed nHA scaffolds may make effective biomimetic environments for studying BrCa bone metastasis.

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