Planta Med 2015; 81 - PM_54
DOI: 10.1055/s-0035-1565431

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

K Kuchta 1, Y Xiang 2, S Huang 2, Y Tang 2, X Peng 2, X Wang 2, Y Zhu 2, J Li 2, J Xu 2, Z Lin 2, T Pan 2
  • 1National Institute of Health Sciences, Division of Pharmacognosy, Phytochemistry and Narcotics, Setagaya-ku, Kamiyoga 1 – 18 – 1, 158 – 8501 Tokyo, Japan, Tokyo, Japan
  • 2Department of Orthopaedic Surgery & Orthopaedic Research Institute, Sun Yat-sen University, 510655 Guangzhou, China, Guangzhou, China

Prostate cancer (PCa) is one of the most common malignant tumours and a leading cause of cancer deaths. Treatment failure of PCa is often due to bone metastasis. Celastrol, an active constituent of the roots of Tripterygium wilfordii Hook.f., has shown anti-tumour effects in previous studies in accordance with its traditional use in China [1]. Here we report for the first time an in-depth study of the effects of celastrol on PCa bone metastasis and its mechanism of action. Using a PC-3 cell model, in vitro assays were performed to evaluate the effects of celastrol on proliferation, migration (wound healing assay), invasion of healthy tissues (Transwell-Matrigel penetration assay), and secretion of Vascular Endothelial Growth Factor (VEGF) (ELISA assay). An intra-tibia injection mouse model was used to assess the effect of celastrol treatment on PCa bone metastasis in vivo. Pre-treatment with celastrol significantly reduced proliferation of PC-3 cells in a dose-dependent manner and cell migration was much slower than in untreated controls. In the penetration assay, significantly fewer cells penetrated through the gel-membrane after celastrol administration and their skeletal invasive ability was also significantly reduced in a dose-dependent manner. Correspondingly, a significant, dose dependent decrease in VEGF secretion was observed. In the in vivo mouse model, pre-treatment with celastrol (8 µmol/L) inhibited the tumourigenicity of PC-3 cells so that almost no bone invasion occurred as compared to control injections. Histological examinations using H&E-staining showed that tibiae injected with celastrol pre-treated PC-3 cells retained their natural bone structure. Our results suggest that celastrol may have major preventive potential against PCa bone metastasis.

References:

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