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.

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.

• Authors: Sun Kyoung Lee, Kwang-Kyun Park, Hyun-Jeong Kim, Ki Rim Kim, Eun Ji Kang, Yu Li Kim, Heein Yoon, Yeong Shik Kim, Won-Yoon Chung
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 36 Issue 5 Pg. 1809-20 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 26184636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Saponins
• Transcription Factors
• Triterpenes
• platycodin D

Topics

• 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, pathology)
• Saponins (pharmacology)
• Transcription Factors (antagonists & inhibitors)
• Triterpenes (pharmacology)