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

 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. 
 Cellular Physiology and Biochemistry, Vol.36(5) : 1809-1820, 2015 
Journal Title
 Cellular Physiology and Biochemistry 
Issue Date
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.
Appears in Collections:
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소)
Yonsei Authors
강은지(Kang, Eun Ji) ; 김기림(Kim, Ki Rim) ; 김유리(Kim, Yu Li) ; 김현정(Kim, Hyun Jeong) ; 박광균(Park, Kwang Kyun) ; 윤희인(Yoon, Hee In) ; 이선경(Lee, Sun Kyung) ; 정원윤(Chung, Won Yoon)
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