Molecular Mechanism(s) Involved in 25-Hydroxyvitamin D's Antiproliferative Effects in CYP27B1-transfected LNCaP Cells

Anticancer Res. 2015 Jul;35(7):3773-9.

Abstract

Background/aim: 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.

Materials and 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.

Conclusion: The present study supports the hypothesis that local production of 1α,25(OH)2D is important in inhibiting prostate cancer development and growth.

Keywords: CYP27B1; LNCaP; Vitamin D.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism*
  • Apoptosis / drug effects
  • Calcitriol / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • G1 Phase / drug effects
  • Humans
  • Male
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Transfection / methods
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacology

Substances

  • Vitamin D
  • 25-hydroxyvitamin D
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human
  • Calcitriol