Does the inhibition of c-myc expression mediate the anti-tumor activity of PPAR's ligands in prostate cancer cell lines?

Arch Biochem Biophys. 2007 Jun 1;462(1):1-12. doi: 10.1016/ Epub 2007 Apr 5.


Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands seem to induce anticancer effects on prostate cancer cells, but the mechanism is not clear. The effect of PPARgamma ligands omega-6 fatty acids and ciglitazone (2-15 microM)--on proliferation, and apoptosis of LNCaP, PC-3, DU145, CA-K and BPH-K cells was studied. PPARgamma ligands led to: (1) reduction of proliferation (20-50%) of all the studied cell lines, (2) stimulation of differentiation of prostate cancer cells through an increased expression (1.5-3-fold: LNCaP, DU145, BPH-K) or reexpression (PC-3, CA-K) of E-cadherin with parallel inhibition of N-cadherin expression (PC-3, CA-K) and (3) down-regulation (1-2-fold) of beta-catenin and c-myc expression. The selective PPARgamma antagonist GW9662 abolished the effect of those ligands on prostate cancer cells. These results suggest that inhibition of beta-catenin and in effect c-myc expression through activation of PPARgamma may help prostate cancer cells to restore several characteristics of normal prostate cells phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cadherins / metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Linoleic Acid / pharmacology
  • Male
  • PPAR gamma / metabolism*
  • Prostatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors*
  • Thiazolidinediones / pharmacology
  • beta Catenin / metabolism*


  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Antineoplastic Agents
  • Cadherins
  • MYC protein, human
  • PPAR gamma
  • Proto-Oncogene Proteins c-myc
  • Thiazolidinediones
  • beta Catenin
  • Linoleic Acid
  • ciglitazone