PPARβ-Mediated Suppression of the Growth and Survival in Human Myeloma Cells Conteracting NF-kB Activity.

Abstract

PPAR(peroxisomal proliferators-activated receptor)β is considered to be involved in the lipid metabolism and regulating the inflammatory response and in human myeloma cells PPARβis predominantly expressed among these PPARs. However, it remains to be clarified what is the functional role of PPARβ in myeloma cells. In order to identify what are the ligands for PPARβ, we constructed the PPREβ-luciferase reporter gene and performed the reporter assay in Hela cells. Since we have already identified several reagents (DHEA (dehydroepiandrosterone), DHEA-S, baicalein, baicalin, dexamethasone) that suppressed the growth or survival of human myeloma cells (Cancer Res 65:2269, 2005; Blood 105:3312, 2005), we analyzed whether these reagents augmented the expression of reporter gene. DHEA-S, baicalein and dexamethasone showed the possibility of their PPARβ binding. Furthermore, these reagents could induce or upregulate the expression of PPREβ-target genes such as ILK and COX2 in myeloma cell lines. We've already confirmed that DHEA-S inhibited the proliferation and survival of primary myeloma cells as well as myeloma cell lines, and downregulated the activity of NF-kB, also baicalein showed the growth suppression through the downregulation of NF-kB. Therefore, it is possible that PPARβ-binding reagents such as DHEA-S and baicalein could counteract NF-kB activity to suppress the growth or survival in myeloma cells, while the exact mechanism is under investigation.