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Raddeanoside R13 inhibits breast cancer cell proliferation, invasion, and metastasis

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Tumor Biology

Abstract

Pulsatilla chinensis is one of the 50 famous fundamental herbs used in traditional Chinese medicine. Saponins are the main components of P. chinensis. Although the anti-proliferative function of saponins has been established in plenty types of cancer, the role of saponins on tumor invasion and metastasis has not been reported, and the mechanisms of how saponins exert the anti-tumor functions are still poorly characterized. Here, we demonstrate that, in breast cancer (BC) cells, raddeanoside R13, a component of saponins extracted from P. chinensis, exhibits strong anti-proliferative and anti-metastasis ability, accompanied by cell cycle arrest, apoptosis, autophagy, and reversion of epithelial-mesenchymal transition (EMT). Raddeanoside R13 (R13) inhibits BC cell proliferation via the activation of G1/S checkpoint transitions, concomitant with a marked decrease of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. R13 induces BC cell apoptosis accompanied by the increased levels of cleaved PARP and caspase-3. R13 inhibits BC cell migration and invasion and regulates the expression of the markers of EMT, which plays a critical role in cancer cell migration and invasion. Moreover, R13 suppresses BC tumor growth and metastasis in nude mice. These data highlight the important role of R13 in BC cell proliferation and progression and suggest that R13 may be a useful drug for BC therapy.

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Acknowledgments

The work was supported by the National Key Subject of Drug Innovation (2011ZX11102), Jiangxi province predominant science and technology innovation project (2010DQB01700), National Natural Science Foundation (81330053, 81272913, 81472589, and 31100604), and Beijing Nova Program (Z141102001814055). Beijing University of Chinese Medicine and Beijing Institute of Biotechnology contributed equally to this work.

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    Authors and Affiliations

    1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, 6 Central Ring South Rd, Beijing, 100102, China

      Yingchun Liang & Shilin Yang

    2. Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing, 100850, People’s Republic of China

      Xiaojie Xu, Ling Li, Tian Hong, Quanbo Ji, Shuai Jin, Yeqiong Song, Jing Guo & Qinong Ye

    3. Jiangxi University of Traditional Chinese Medicine, Nanchang, China

      Xiaojie Xu, Yulin Feng & Shilin Yang

    4. 401 Hospital of PLA Liberation Army, Qingdao, China

      Haiming Yu

    5. Laboratory of Computer-aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China

      Zhibing Zheng

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    1. Yingchun Liang
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    Correspondence to Zhibing Zheng, Qinong Ye or Shilin Yang.

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    Animal studies were approved by the Institutional Animal Care Committee of Beijing Institute of Biotechnology.

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    Yingchun Liang, Xiaojie Xu and Haiming Yu contributed equally to this work.

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    Liang, Y., Xu, X., Yu, H. et al. Raddeanoside R13 inhibits breast cancer cell proliferation, invasion, and metastasis. Tumor Biol. 37, 9837–9847 (2016). https://doi.org/10.1007/s13277-015-4748-5

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    • DOI: https://doi.org/10.1007/s13277-015-4748-5

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