Cholesterol and phytosterols differentially regulate the expression of caveolin 1 and a downstream prostate cell growth-suppressor gene

Cancer Epidemiol. 2010 Aug;34(4):461-71. doi: 10.1016/j.canep.2010.04.009. Epub 2010 May 12.


Background: The purpose of our study was to show the distinction between the apoptotic and anti-proliferative signaling of phytosterols and cholesterol-enrichment in prostate cancer cell lines, mediated by the differential transcription of caveolin-1, and N-myc downstream-regulated gene 1 (NDRG1), a pro-apoptotic androgen-regulated tumor suppressor.

Methods: PC-3 and DU145 cells were treated with sterols (cholesterol and phytosterols) for 72h, followed by trypan blue dye-exclusion measurement of necrosis and cell growth measured with a Coulter counter. Sterol induction of cell growth-suppressor gene expression was evaluated by mRNA transcription using RT-PCR, while cell cycle analysis was performed by FACS analysis. Altered expression of Ndrg1 protein was confirmed by Western blot analysis. Apoptosis was evaluated by real time RT-PCR amplification of P53, Bcl-2 gene and its related pro- and anti-apoptotic family members.

Results: Physiological doses (16microM) of cholesterol and phytosterols were not cytotoxic in these cells. Cholesterol-enrichment promoted cell growth (P<0.05), while phytosterols significantly induced growth-suppression (P<0.05) and apoptosis. Cell cycle analysis showed that contrary to cholesterol, phytosterols decreased mitotic subpopulations. We demonstrated for the first time that cholesterols concertedly attenuated the expression of caveolin-1 (cav-1) and NDRG1 genes in both prostate cancer cell lines. Phytosterols had the opposite effect by inducing overexpression of cav-1, a known mediator of androgen-dependent signals that presumably control cell growth or apoptosis.

Conclusions: Cholesterol and phytosterol treatment differentially regulated the growth of prostate cancer cells and the expression of p53 and cav-1, a gene that regulates androgen-regulated signals. These sterols also differentially regulated cell cycle arrest, downstream pro-apoptotic androgen-regulated tumor suppressor, NDRG1 suggesting that cav-1 may mediate pro-apoptotic NDRG1 signals. Elucidation of the mechanism for sterol modulation of growth and apoptosis signaling may reveal potential targets for cancer prevention and/or chemotherapeutic intervention. Sterol regulation of NDRG1 transcription suggests its potential as biomarker for prediction of neoplasms that would be responsive to chemoprevention by phytosterols.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Caveolin 1 / genetics*
  • Caveolin 1 / metabolism
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation / drug effects
  • Cholesterol / pharmacology*
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Phytosterols / pharmacology*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • CAV1 protein, human
  • Caveolin 1
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein
  • Phytosterols
  • RNA, Messenger
  • Cholesterol