title: Molecular Mechanism(s) Involved in 25-Hydroxyvitamin D's Antiproliferative Effects in CYP27B1-transfected LNCaP Cells.
abstract: OBJECTIVE
  1α,25(OH)2D has been shown to induce cell-cycle regulation, apoptosis and differentiation in prostate cancer cells. Previous studies have demonstrated that prostate and some prostate cancer cells have the ability to convert 25(OH)D3 to 1α,25(OH)2D3. The aim of the present study was to elucidate the role of 1α,25(OH)2D3 production by 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) on prostate cancer cell growth.
  
  
  METHODS
  LNCaP cells were stably transfected with CYP27B.
  
  
  RESULTS
  Stably-transfected 1α-OHase LNCaP cells converted 25(OH)D3 to 1α,25(OH)2D3 unlike untransfected LNCaP cells. There was a dose-dependent decrease in (3)H-thymidine incorporation in 1α,25(OH)2D3-treated LNCaP cells, not seen with 25(OH)D3 treatment, and in stably transfected 1α-OHase LNCaP cells treated with 25(OH)D3. 1α,25(OH)2D3-treated LNCaP cells and 25(OH)D3-treated stably-transfected 1α-OHase LNCaP cells demonstrated an increased G1 phase accumulation and apoptosis, while 25(OH)D3 treatment had no effect in LNCaP cells.
  
  
  CONCLUSIONS
  The present study supports the hypothesis that local production of 1α,25(OH)2D is important in inhibiting prostate cancer development and growth.
authors.affiliation: Vitamin D, Skin and Bone Research Laboratory, Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A.
authors.forename: Mara
authors.initials: M
authors.lastname: Banks
authors.affiliation: Vitamin D, Skin and Bone Research Laboratory, Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A. mfholick@bu.edu.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Holick
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics; D014162:Transfection / Q000379:methods; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human; D002117:Calcitriol
keywords: CYP27B1; LNCaP; Vitamin D