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Platycodin D Blocks Breast Cancer-Induced Bone Destruction by Inhibiting Osteoclastogenesis and the Growth of Breast Cancer Cells

Authors
 Lee S.K. ; Park K.-K. ; Chung W.-Y. ; Kim Y.S. ; Yoon H. ; Kim Y.L. ; Kang E.J. ; Kim K.R. ; Kim H.-J. 
Citation
 Cellular Physiology and Biochemistry, Vol.36(5) : 1809~1820, 2015 
Journal Title
 Cellular Physiology and Biochemistry 
ISSN
 1015-8987 
Issue Date
2015
Abstract
BACKGROUND: Metastatic breast cancer cells are frequently associated with osteoclast-mediated bone resorption, resulting in severe bone destruction and increased mortality in patients. Platycodin D (PD) isolated from Platycodon grandiflorum is a triterpenoid saponin with anti-cancer and anti-angiogenic potential. METHODS: The in vivo activity was determined in mice with the intratibial injection of human metastatic breast cancer cells. Osteoclast formation and activity were detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates. The expression of osteoclastogenesis-inducing molecules was detected by RT-PCR and western blotting in RANKL-treated bone marrow macrophages (BMMs). Cell viability and DNA synthesis were measured with MTT and BrdU incorporation assays. The induction of apoptosis was estimated using TUNEL staining and a caspase-3 activity assay. RESULTS: The oral administration of PD inhibited MDA-MB-231 cell-induced osteolysis in an intratibial mouse model. PD treatment blocked RANKL-induced osteoclast formation by inhibiting the expression and nuclear translocation of NFATc1 and c-Fos in BMMs and consequently reduced osteoclast-mediated bone resorption. Furthermore, PD treatment induced apoptosis in osteoclasts and inhibited the growth of MDA-MB-231 cells. CONCLUSION: PD may block breast cancer-induced bone loss by suppressing the formation, activity, and survival of osteoclasts, as well as the growth of metastatic breast cancer cells.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/140635
Appears in Collections:
1. 연구논문 > 2. College of Dentistry > Dept. of Oral Biology
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 5. Research Institutes > Oral Cancer Research Institute
Yonsei Authors
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 http://www.karger.com/Article/FullText/430152
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