p53 Is required for 1,25-dihydroxyvitamin D3-induced G0 arrest but is not required for G1 accumulation or apoptosis of LNCaP prostate cancer cells

Endocrinology. 2003 Jan;144(1):50-60. doi: 10.1210/en.2001-210109.


1,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] is an effective agent for inhibiting the growth of prostate cancer cells including LNCaP and PC-3 cell lines. However, the extent of growth inhibition in these cell lines differs because LNCaP cells are much more responsive than PC-3 cells. Previous studies in LNCaP cells have shown that 1,25-(OH)(2)D(3) treatment results in G(0)/G(1) cell cycle accumulation, loss of Ki67 expression, and induction of apoptosis. One difference between the two cell lines is that PC-3 cells lack functional p53, a protein that plays roles both in cell cycle regulation and induction of apoptosis. In this study, the role of p53 in 1,25-(OH)(2)D(3) action was examined using the p53-negative PC-3 cells and a line of LNCaP cells, called LN-56, in which p53 function was shut off using a dominant negative p53 fragment. We found that treatment with 1,25-(OH)(2)D(3) extensively inhibits growth of LN-56 prostate cancer cells lacking p53, but in contrast to the parental LNCaP cells, the LN-56 cells recover rapidly. Moreover, in prostate cancer cells, the synergism between 1,25-(OH)(2)D(3) and 9-cis retinoic acid appears to be dependent on the presence of functional p53; however, 1,25-(OH)(2)D(3)-mediated induction of G(1) cell cycle accumulation and induction of apoptosis is not.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alitretinoin
  • Apoptosis / drug effects*
  • Calcitriol / pharmacology*
  • Cell Division / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Drug Synergism
  • G1 Phase / drug effects*
  • Humans
  • Ki-67 Antigen / analysis
  • Male
  • Prostatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Resting Phase, Cell Cycle / drug effects*
  • Tretinoin / pharmacology
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology*


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Alitretinoin
  • Tretinoin
  • Calcitriol