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

Peroxisome proliferator-activated receptor gamma (PPARγ) ligands seem to induce anticancer effects on prostate cancer cells, but the mechanism is not clear. The effect of PPARγ ligands ω-6 fatty acids and ciglitazone (2–15 μM)—on proliferation, and apoptosis of LNCaP, PC-3, DU145, CA-K and BPH-K cells was studied. PPARγ 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 β-catenin and c-myc expression. The selective PPARγ antagonist GW9662 abolished the effect of those ligands on prostate cancer cells. results suggest that inhibition of β-catenin and in effect c-myc expression through activation of PPARγ may help prostate cancer cells to restore several characteristics of normal prostate cells phenotype.