BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is expressed in certain human cancers. Ligand-induced PPAR-gamma activation can result in growth inhibition and differentiation in these cancer cells; however, the precise mechanism for the anti-proliferative effect of PPAR-gamma ligands is not clear. METHODS: In this study, we examined the expression of PPAR-gamma in human prostate cancer and the effect of two PPAR-gamma ligands, 15 deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) and troglitazone, on prostate cancer cell growth. RESULTS: PPAR-gamma is frequently over-expressed in androgen independent prostate cancer cell lines and human prostate cancer tissues (22 of 47; 47%). Both 15d-PGJ2 and troglitazone inhibited proliferation and DNA synthesis of prostate cancer cell lines in a dose-dependent manner, and slightly increased the proportion of cells with S-phase DNA content. Prostate specific antigen (PSA) promoter reporter assays showed that troglitazone and 15d-PGJ2 down-regulated androgen stimulated reporter gene activity in prostate cancer cell lines LNCaP. Interestingly, LNCaP with troglitazone dramatically suppressed PSA protein expression without suppressing AR expression. CONCLUSIONS: Taken together, these results suggest that PPAR-gamma ligands may be a useful therapeutic agent for the treatment of prostate cancer.
BACKGROUND:Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is expressed in certain humancancers. Ligand-induced PPAR-gamma activation can result in growth inhibition and differentiation in these cancer cells; however, the precise mechanism for the anti-proliferative effect of PPAR-gamma ligands is not clear. METHODS: In this study, we examined the expression of PPAR-gamma in humanprostate cancer and the effect of two PPAR-gamma ligands, 15 deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) and troglitazone, on prostate cancer cell growth. RESULTS:PPAR-gamma is frequently over-expressed in androgen independent prostate cancer cell lines and humanprostate cancer tissues (22 of 47; 47%). Both 15d-PGJ2 and troglitazone inhibited proliferation and DNA synthesis of prostate cancer cell lines in a dose-dependent manner, and slightly increased the proportion of cells with S-phase DNA content. Prostate specific antigen (PSA) promoter reporter assays showed that troglitazone and 15d-PGJ2 down-regulated androgen stimulated reporter gene activity in prostate cancer cell lines LNCaP. Interestingly, LNCaP with troglitazone dramatically suppressed PSA protein expression without suppressing AR expression. CONCLUSIONS: Taken together, these results suggest that PPAR-gamma ligands may be a useful therapeutic agent for the treatment of prostate cancer.
Authors: Kasem Nithipatikom; Marilyn A Isbell; Michael P Endsley; Jeffrey E Woodliff; William B Campbell Journal: Prostaglandins Other Lipid Mediat Date: 2010-12-15 Impact factor: 3.072
Authors: Mao Song Lin; Jun Xing Huang; Wei Chang Chen; Bao Feng Zhang; Jing Fang; Qiong Zhou; Ying Hu; Heng Jun Gao Journal: Oncol Lett Date: 2011-09-06 Impact factor: 2.967