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Prostate Cancer Prostatic Dis. 2017 Jun;20(2):156-164. doi: 10.1038/pcan.2016.61. Epub 2017 Feb 14.

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

Author information

1
Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
2
Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

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.

PMID:
28195223
DOI:
10.1038/pcan.2016.61
[Indexed for MEDLINE]

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