Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines.
The development of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPARbeta/delta promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPARbeta/delta ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPARbeta/delta on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPARbeta/delta ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPARbeta/delta target gene angiopoietin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPARbeta/delta inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPARbeta/delta ligands are not mitogenic in human cancer cell lines.
Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA.
Elizabeth E
EE
Girroir
Holly E
HE
Hollingshead
Andrew N
AN
Billin
Timothy M
TM
Willson
Gavin P
GP
Robertson
Arun K
AK
Sharma
Shantu
S
Amin
Frank J
FJ
Gonzalez
Jeffrey M
JM
Peters
D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016895:Culture Media, Serum-Free; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008024:Ligands; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D010636:Phenols; D013438:Sulfhydryl Compounds
D016895:Culture Media, Serum-Free; D008024:Ligands; D047494:PPAR delta; D048068:PPAR-beta; D013844:Thiazoles; C425931:GW 501516; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds