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Basic Research

Celastrol, an active constituent of the TCM plant Tripterygium wilfordii Hook.f., inhibits prostate cancer bone metastasis

Prostate Cancer and Prostatic Diseases volume 20, pages 156–164 (2017)Cite this article

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An Erratum to this article was published on 28 March 2017

Abstract

Background:

Treatment failure of prostate cancer (PCa) is often due to bone metastasis. Celastrol, an active constituent of Tripterygium wilfordii roots, has shown anti-tumor effects in previous studies in accordance with its indication in traditional Chinese medicine.

Methods:

Using a PC-3 cell model, in vitro assays were performed to evaluate the effects of celastrol on proliferation, migration (wound healing assay), tissues invasion (Transwell–Matrigel penetration assay) and vascular endothelial growth factor (VEGF) secretion (enzyme-linked immunosorbent assay). An intra-tibia injection mouse model was used to assess the effect of celastrol on PCa bone metastasis in vivo.

Results:

Pretreatment with celastrol significantly reduced proliferation of PC-3 cells in a dose-dependent manner and cell migration was much slower than in controls. Significantly fewer cells penetrated the gel-membrane after celastrol administration and their skeletal invasive ability was significantly reduced in a dose-dependent manner. Correspondingly, a significant, dose-dependent decrease in VEGF secretion was observed. In the in vivo mouse model, pretreatment with celastrol (8 μmol l−1) inhibited the tumorigenicity of PC-3 cells so that almost no bone invasion occurred as compared with control injections. Histological examinations using hematoxylin and eosin staining showed that tibiae injected with celastrol pretreated PC-3 cells retained their natural bone structure.

Conclusions:

Celastrol may have preventive potential against PCa bone metastasis.

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Acknowledgements

Dedicated to the memory of my friend and mentor Professor Dr Adolf Nahrstedt, Chair of Pharmacognosy at Münster University, Germany, who died on 7 January 2016 after a long battle with prostate cancer. This work was supported by the ‘Key Science and Technology Planning Project of Guangzhou’ Grant (2009A1-E031-3) and ‘Sino-Japanese scientific and technological cooperation program, MOST of China’ (No. 198-59).

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Authors and Affiliations

  1. Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan,

    K Kuchta

  2. Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Y Xiang, S Huang, Y Tang, X Peng, X Wang, Y Zhu, J Li, J Xu, Z Lin & T Pan

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  1. K Kuchta
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Correspondence to K Kuchta or T Pan.

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Kuchta, K., Xiang, Y., Huang, S. et al. Celastrol, an active constituent of the TCM plant Tripterygium wilfordii Hook.f., inhibits prostate cancer bone metastasis. Prostate Cancer Prostatic Dis 20, 156–164 (2017). https://doi.org/10.1038/pcan.2016.61

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