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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.  ;  Kim H.-J.  ;  Kim K.R.  ;  Kang E.J.  ;  Kim Y.L.  ;  Yoon H.  ;  Kim Y.S.  ;  Chung W.-Y. 
Citation
 CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, Vol.36(5) : 1809-1820, 2015 
Journal Title
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
ISSN
 1015-8987 
Issue Date
2015
MeSH
Animals ; Apoptosis/drug effects ; Bone and Bones/pathology* ; Breast Neoplasms/pathology* ; Cell Division/drug effects* ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Osteoclasts/drug effects* ; Osteoclasts/pathology ; Saponins/pharmacology* ; Transcription Factors/antagonists & inhibitors ; Triterpenes/pharmacology*
Keywords
Platycodin D ; Breast cancer ; Osteoclastogenesis ; Bone destruction
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.
Full Text
http://www.karger.com/Article/FullText/430152
DOI
10.1159/000430152
Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Ji(강은지)
Kim, Ki Rim(김기림)
Kim, Yu Li(김유리)
Kim, Hyun-Jeong(김현정) ORCID logo https://orcid.org/0000-0003-4608-2120
Park, Kwang Kyun(박광균)
Yoon, Hee In(윤희인)
Lee, Sun Kyoung(이선경) ORCID logo https://orcid.org/0000-0002-3707-8050
Chung, Won Yoon(정원윤) ORCID logo https://orcid.org/0000-0001-8428-9005
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140635
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