1alpha,25-dihydroxyvitamin D3 actions in LNCaP human prostate cancer cells are androgen-dependent

Endocrinology. 1997 Aug;138(8):3290-8. doi: 10.1210/endo.138.8.5328.


We and others have recently shown that 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] significantly inhibits cell proliferation and increases secretion of prostate-specific antigen (PSA) in LNCaP cells, an androgen-responsive human prostate cancer cell line. The present study was designed to investigate the possible interactions between 1,25-(OH)2D3 and androgens in the regulation of LNCaP cellular function. LNCaP cell growth was dose-dependently inhibited by 1,25-(OH)2D3 (60% inhibition at 10 nM) when cells were cultured in medium supplemented with FBS (FBS medium). 1,25-(OH)2D3-treated cells showed a 5-fold increase in PSA secretion, similar to the increase seen in dihydrotestosterone (DHT)-treated cells. In combination, 1,25-(OH)2D3 and DHT synergistically enhanced PSA secretion 22-fold. This synergistic effect was even greater when cells were cultured in medium supplemented with charcoal-stripped serum (CSS medium), where endogenous steroids are substantially depleted. Under these conditions, 1,25-(OH)2D3 and DHT together stimulated PSA secretion up to 50-fold over the untreated control. Radioligand binding assays and Western blot analyses showed that the androgen receptor (AR) content was increased significantly by 1,25-(OH)2D3 at 48 h. Furthermore, the steady-state mRNA level of AR was up-regulated approximately 2-fold by 1,25-(OH)2D3 at 24 h. When cells were grown in CSS medium, 1,25-(OH)2D3 alone no longer inhibited cell growth or induced PSA secretion. Titration experiments revealed that the addition of DHT at 1 nM to the medium restored the antiproliferative activity of 1,25-(OH)2D3. Conversely, an antiandrogen, Casodex, completely blocked 1,25-(OH)2D3 antiproliferative and PSA stimulation activities when cells were cultured in FBS medium. In conclusion, these results demonstrate that the antiproliferative and PSA induction activities of 1,25-(OH)2D3 in LNCaP cells are dependent upon androgen action and that AR up-regulation by 1,25-(OH)2D3 likely contributes to the synergistic actions of 1,25-(OH)2D3 and DHT in these cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Androgen Antagonists / pharmacology
  • Androgens / pharmacology*
  • Anilides / pharmacology
  • Blotting, Northern
  • Blotting, Western
  • Calcitriol / pharmacology*
  • Cell Division / drug effects
  • Dihydrotestosterone / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Male
  • Neoplasms, Hormone-Dependent / chemistry
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / pathology*
  • Nitriles
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / analysis
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / physiology
  • Tosyl Compounds
  • Tritium
  • Tumor Cells, Cultured
  • Up-Regulation


  • Androgen Antagonists
  • Androgens
  • Anilides
  • Nitriles
  • Receptors, Androgen
  • Tosyl Compounds
  • Dihydrotestosterone
  • Tritium
  • bicalutamide
  • Prostate-Specific Antigen
  • Calcitriol