title: Platycodin D Blocks Breast Cancer-Induced Bone Destruction by Inhibiting Osteoclastogenesis and the Growth of Breast Cancer Cells.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Sun Kyoung
authors.initials: SK
authors.lastname: Lee
authors.forename: Kwang-Kyun
authors.initials: KK
authors.lastname: Park
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ki Rim
authors.initials: KR
authors.lastname: Kim
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kang
authors.forename: Yu Li
authors.initials: YL
authors.lastname: Kim
authors.forename: Heein
authors.initials: H
authors.lastname: Yoon
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Won-Yoon
authors.initials: WY
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001842:Bone and Bones / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D012503:Saponins / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D012503:Saponins; D014157:Transcription Factors; D014315:Triterpenes; C108953:platycodin D