α-Tocopheryl Succinate Inhibits Osteolytic Bone Metastasis of Breast Cancer by Suppressing Migration of Cancer Cells and Receptor Activator of Nuclear Factor-κB Ligand Expression of Osteoblasts
Journal of Bone Metabolism
;
: 23-33, 2018.
Article
in English
| WPRIM
| ID: wpr-740469
ABSTRACT
BACKGROUND:
Breast cancer is one of the most common cancers affecting women and has a high incidence of bone metastasis, causing osteolytic lesions. The elevated expression of receptor activator of nuclear factor-κB ligand (RANKL) in cancer activates osteoclasts, leading to bone destruction. We previously reported that α-tocopheryl succinate (αTP-suc) inhibited interleukin-1-induced RANKL expression in osteoblasts. Here, we examined the effect of αTP-suc on osteolytic bone metastasis in breast cancer.METHODS:
To examine the effect of αTP-suc on the metastatic capacity of breast cancer, MDA-MB-231-FL cells were injected into the left cardiac ventricle of BALB/c nude mice along with intraperitoneal injection of αTP-suc. The mice were then analyzed by bioluminescence imaging. To investigate the effect of αTP-suc on osteolysis, 4T1 cells were directly injected into the femur of BALB/c mice along with intraperitoneal injection of αTP-suc. Microcomputed tomography analysis and histomorphometric analysis of the femora were performed.RESULTS:
αTP-suc inhibited cell migration and cell growth of 4T1 cells. In line with these results, bone metastasis of MDA-MB-231-FL cells was reduced in mice injected with αTP-suc. In addition, αTP-suc decreased osteoclastogenesis by inhibiting 4T1-induced RANKL expression in osteoblasts. Consistent with these results, 4T1-induced bone destruction was ameliorated by αTP-suc, with in vivo analysis showing reduced tumor burden and osteoclast numbers.CONCLUSIONS:
Our findings suggest that αTP-suc may be efficiently utilized to prevent and treat osteolytic bone metastasis of breast cancer with dual effects.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Osteoblasts
/
Osteoclasts
/
Osteolysis
/
Breast
/
Breast Neoplasms
/
Cell Movement
/
Incidence
/
Succinic Acid
/
Tumor Burden
/
X-Ray Microtomography
Type of study:
Incidence study
/
Prognostic study
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Journal of Bone Metabolism
Year:
2018
Type:
Article
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