title: Effect of celastrol on growth inhibition of prostate cancer cells through the regulation of hERG channel in vitro.
abstract: OBJECTIVE
  To explore the antiprostate cancer effects of Celastrol on prostate cancer cells' proliferation, apoptosis, and cell cycle distribution, as well as the correlation to the regulation of hERG.
  
  
  METHODS
  DU145 cells were treated with various concentrations of Celastrol (0.25-16.0 μmol/L) for 0-72 hours. MTT assay was used to evaluate the inhibition effect of Celastrol on the growth of DU145 cells. Cell apoptosis was detected through both Annexin-V FITC/PI double-labeled cytometry and Hoechst 33258. Cell cycle regulation was examined by a propidium iodide method. Western blot and RT-PCR technologies were applied to assess the expression level of hERG in DU145 cells.
  
  
  RESULTS
  Celastrol presented striking growth inhibition and apoptosis induction potency on DU145 cells in vitro in a time- and dose-dependent manner. The IC50 value of Celastrol for 24 hours was 2.349 ± 0.213 μmol/L. Moreover, Celastrol induced DU145 cell apoptosis in a cell cycle-dependent manner, which means Celastrol could arrest DU145 cells in G0/G1 phase; accordingly, cells in S phase decreased gradually and no obvious changes were found in G2/M phase cells. Through transmission electron microscope, apoptotic bodies containing nuclear fragments were found in Celastrol-treated DU145 cells. Overexpression of hERG channel was found in DU145 cells, while Celastrol could downregulate it at both protein and mRNA level in a dose-dependent manner (P < 0.01).
  
  
  CONCLUSIONS
  Celastrol exhibits its antiprostate cancer effects partially through the downregulation of the expression level of hERG channel in DU145 cells, suggesting that Celastrol may be a potential agent against prostate cancer with a mechanism of blocking the hERG channel.
authors: Medical College, Wuhan University of Science and Technology, Wuhan 430065, China ; The Outpatient Department, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors: Nan
authors: N
authors: Ji
authors: Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors: Jinjun
authors: J
authors: Li
authors: Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 430081, China.
authors: Zexiong
authors: Z
authors: Wei
authors: Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 430081, China.
authors: Fanhu
authors: F
authors: Kong
authors: Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 430081, China.
authors: Hongyan
authors: H
authors: Jin
authors: Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors: Xiaoya
authors: X
authors: Chen
authors: Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60121, USA.
authors: Yan
authors: Y
authors: Li
authors: Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors: Youping
authors: Y
authors: Deng
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D053978:Pentacyclic Triterpenes; D011471:Prostatic Neoplasms; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D009363:Neoplasm Proteins; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol