Peroxisome proliferator-activated receptor-gamma and growth inhibition by its ligands in prostate cancer.
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.
Nagata
Daisuke
D
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan.
Yoshihiro
Hashimoto
H
Nakanishi
Makoto
M
Naruyama
Hiromichi
H
Okada
Shinsuke
S
Ando
Ryosuke
R
Tozawa
Keiichi
K
Kohri
Kenjiro
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D047495:PPAR gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D014162:Transfection; D000077288:Troglitazone
C477819:15-deoxyprostaglandin J2; D000970:Antineoplastic Agents; D002839:Chromans; D008024:Ligands; D047495:PPAR gamma; D011944:Receptors, Androgen; D045162:Thiazolidinediones; D017430:Prostate-Specific Antigen; D000077288:Troglitazone; D015230:Prostaglandin D2