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 (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.
Laidler
Piotr
P
Chair of Medical Biochemistry, Jagiellonian University Medical College, 31-034 Krakow, ul Kopernika 7, Poland. mblaidle@cyf-kr.edu.pl
Dulińska
Joanna
J
Mrozicki
Sławomir
S
D000813:Anilides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D008297:Male; D047495:PPAR gamma / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors*; D045162:Thiazolidinediones / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000970:Antineoplastic Agents; D015820:Cadherins; C489427:MYC protein, human; D047495:PPAR gamma; D016271:Proto-Oncogene Proteins c-myc; D045162:Thiazolidinediones; D051176:beta Catenin; D019787:Linoleic Acid; C039671:ciglitazone