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Andrographolide prevents human breast cancer-induced osteoclastic bone loss via attenuated RANKL signaling

Abstract

Bone metastasis is a common and serious complication in advanced cancers such as breast cancer, prostate cancer, and multiple myeloma. Agents that prevent bone loss could be used to develop an alternative therapy for bone metastasis. RANKL, a member of the tumor necrosis factor superfamily, has been shown to play a significant role in cancer-associated bone loss. In this study, we examined the efficacy of the natural compound andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata, in reducing breast cancer-induced osteolysis. AP prevented human breast cancer-induced bone loss by suppressing RANKL-mediated and human breast cancer cell-induced osteoclast differentiation. Molecular analysis revealed that AP prevented osteoclast function by inhibiting RANKL-induced NF-κB and ERK signaling pathway in lower dose (20 μM), as well as inducing apoptosis at higher dose (40 μM). Thus, AP is a potent inhibitor of breast cancer-induced bone metastasis.

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Acknowledgments

This work was supported by the Program for Innovative Research Team of Shanghai Municipal Education Commission (Phase I), a grant from the Innovative Research from Shanghai Municipal Education Commission (13YZ031), a grant for scientific research from the National Natural Science Foundation for the Youth of China (No. 81201364), grant from the scientific research foundation for returned overseas Chinese scholars from the state human resource ministry, the Key National Basic Research Program of China (Grant No. 2012CB619101), a scientific research grant for youth of Shanghai (Grant No. ZZjdyx 2097), a scientific research grant from 985 project--stem cell and regenerative medicine centre, a scientific research grant from Zhejiang National Science Foundation (Grant No.Y2110653), and the Major Basic Research of Science and Technology Commission of Shanghai Municipality (Grant No. 11DJ1400303).

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The authors declare that they have no conflict of interest.

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Correspondence to An Qin or Kerong Dai.

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Zanjing Zhai, Xinhua Qu and Wei Yan have contributed equally to this study.

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Zhai, Z., Qu, X., Yan, W. et al. Andrographolide prevents human breast cancer-induced osteoclastic bone loss via attenuated RANKL signaling. Breast Cancer Res Treat 144, 33–45 (2014). https://doi.org/10.1007/s10549-014-2844-7

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Keywords

  • Andrographolide
  • RANKL
  • Osteoclast
  • Breast cancer
  • Bone metastasis