PPARgamma agonists attenuate proliferation and modulate Wnt/beta-catenin signalling in melanoma cells.

Abstract

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear hormone receptor (NHR) superfamily of ligand-activated transcriptional regulators. Accumulating evidence suggests that PPARgamma agonists such as the thiazolidinediones (TZDs) may prove to be useful anti-cancer agents exhibiting anti-proliferative and/or pro-apoptotic affects in a range of cancer cell types including melanoma, however, the mechanisms underlying this effect remain unclear. We have demonstrated the anti-proliferative effects of full and partial PPARgamma modulators in human melanoma cell lines. Ablation of PPARgamma expression in the MM96L melanoma cell line by siRNA mediated mechanisms attenuates the anti-proliferative effect of these agents suggesting this effect is directly mediated by PPARgamma. The mechanisms underlying the anti-proliferative effects of PPARgamma in melanoma cells involve the regulation of expression of a number of critical cell cycle genes and beta-catenin. Moreover, our data indicate that PPARgamma modulates Wnt/beta-catenin mediated signalling in melanoma cells in an agonist dependent manner.

• Authors: Aaron G Smith, Kimberley A Beaumont, Darren J Smit, Amy E Thurber, Anthony L Cook, Glen M Boyle, Peter G Parsons, Richard A Sturm, George E O Muscat
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 41 Issue 4 Pg. 844-52 (Apr 2009) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 18822385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Chromans
• PPAR gamma
• RNA, Messenger
• RNA, Small Interfering
• Thiazolidinediones
• Wnt Proteins
• beta Catenin
• Rosiglitazone
• Troglitazone
• Halofenate

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• COS Cells
• Cell Cycle (drug effects, genetics)
• Cell Growth Processes (drug effects, physiology)
• Cell Line, Tumor
• Chlorocebus aethiops
• Chromans (pharmacology)
• Halofenate (pharmacology)
• Humans
• Melanoma (drug therapy, genetics, metabolism, pathology)
• PPAR gamma (agonists, biosynthesis, genetics)
• RNA, Messenger (biosynthesis, genetics)
• RNA, Small Interfering (genetics)
• Rosiglitazone
• Signal Transduction (drug effects)
• Thiazolidinediones (pharmacology)
• Troglitazone
• Wnt Proteins (agonists, genetics, metabolism)
• beta Catenin (genetics, metabolism)