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Shin JE, Kim HJ, Kim KR, et al. Type I saikosaponins a and d inhibit osteoclastogenesis in bone marrow-derived macrophages and osteolytic activity of metastatic breast cancer cells. Evid Based Complement Alternat Med. 2015;2015:582437doi: 10.1155/2015/582437.
Shin, J. E., Kim, H. J., Kim, K. R., Lee, S. K., Park, J., Kim, H., Park, K. K., & Chung, W. Y. (2015). Type I saikosaponins a and d inhibit osteoclastogenesis in bone marrow-derived macrophages and osteolytic activity of metastatic breast cancer cells. Evidence-based complementary and alternative medicine : eCAM, 2015582437. https://doi.org/10.1155/2015/582437
Shin, Ji-Eun, et al. "Type I saikosaponins a and d inhibit osteoclastogenesis in bone marrow-derived macrophages and osteolytic activity of metastatic breast cancer cells." Evidence-based complementary and alternative medicine : eCAM vol. 2015 (2015): 582437. doi: https://doi.org/10.1155/2015/582437
Shin JE, Kim HJ, Kim KR, Lee SK, Park J, Kim H, Park KK, Chung WY. Type I saikosaponins a and d inhibit osteoclastogenesis in bone marrow-derived macrophages and osteolytic activity of metastatic breast cancer cells. Evid Based Complement Alternat Med. 2015;2015:582437. doi: 10.1155/2015/582437. Epub 2015 Mar 29. PMID: 25892999; PMCID: PMC4393913.
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Evid Based Complement Alternat Med. 2015;2015:582437. doi: 10.1155/2015/582437. Epub 2015 Mar 29.

Type I saikosaponins a and d inhibit osteoclastogenesis in bone marrow-derived macrophages and osteolytic activity of metastatic breast cancer cells.

Evidence-based complementary and alternative medicine : eCAM

Ji-Eun Shin, Hyun-Jeong Kim, Ki-Rim Kim, Sun Kyoung Lee, Junhee Park, Hyungkeun Kim, Kwang-Kyun Park, Won-Yoon Chung

Affiliations

  1. Department of Applied Life Science, The Graduate School, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea.
  2. Department of Oral Biology, Oral Cancer Research Institute and BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
  3. Department of Oral Biology, Oral Cancer Research Institute and BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea ; Department of Dental Hygiene, Kyungpook National University, Sangju 742-711, Republic of Korea.
  4. Department of Oral Biology, Oral Cancer Research Institute and BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea ; Department of Dentistry, The Graduate School, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea.
  5. Department of Applied Life Science, The Graduate School, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea ; Department of Oral Biology, Oral Cancer Research Institute and BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
  6. Department of Applied Life Science, The Graduate School, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea ; Department of Oral Biology, Oral Cancer Research Institute and BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea ; Department of Dentistry, The Graduate School, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea.

PMID: 25892999 PMCID: PMC4393913 DOI: 10.1155/2015/582437

Abstract

Many osteopenic disorders, including a postmenopausal osteoporosis and lytic bone metastasis in breast and prostate cancers, are linked with a hyperosteoclast activity due to increased receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblastic/stromal cells. Therefore, inhibition of RANKL-induced osteoclastogenesis and osteoclast-induced bone resorption is an important approach in controlling pathophysiology of these skeletal diseases. We found that, of seven type I, II, and III saikosaponins isolated from Bupleurum falcatum, saikosaponins A and D, type I saikosaponins with an allyl oxide linkage between position 13 and 28 and two carbohydrate chains that are directly attached to the hydroxyl groups in position 3, exhibited the most potent inhibition on RANKL-induced osteoclast formation at noncytotoxic concentrations. The stereochemistry of the hydroxyl group at C16 did not affect their activity. Saikosaponins A and D inhibited the formation of resorptive pits by reducing the secreted levels of matrix metalloproteinase- (MMP-) 2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Additionally, saikosaponins A and D inhibited mRNA expression of parathyroid hormone-related protein as well as cell viability and invasion in metastatic human breast cancer cells. Thus, saikosaponins A and D can serve as a beneficial agent for the prevention and treatment of osteoporosis and cancer-induced bone loss.

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