title: Celastrol, an active constituent of the TCM plant Tripterygium wilfordii Hook.f., inhibits prostate cancer bone metastasis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Celastrol may have preventive potential against PCa bone metastasis.
authors.affiliation: Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kuchta
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: T
authors.initials: T
authors.lastname: Pan
mesh_terms: D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D053978:Pentacyclic Triterpenes; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C050414:celastrol