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
10.11005/jbm.2018.25.1.23
- Author:
Bongjun KIM
1
;
Hong Hee KIM
;
Zang Hee LEE
Author Information
1. Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University College of Medicine, Seoul, Korea. zang1959@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Alpha-tocopheryl succinate;
Breast neoplasms;
Osteolysis
- MeSH:
Animals;
Breast Neoplasms;
Breast;
Cell Movement;
Female;
Femur;
Heart Ventricles;
Humans;
Incidence;
Injections, Intraperitoneal;
Mice;
Mice, Nude;
Neoplasm Metastasis;
Osteoblasts;
Osteoclasts;
Osteolysis;
Succinic Acid;
Tumor Burden;
X-Ray Microtomography
- From:Journal of Bone Metabolism
2018;25(1):23-33
- CountryRepublic of Korea
- Language:English
-
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.
