Baicalein Combined with Dexamethasone Can Induce the Marked PPARß-Mediated Suppression of Growth and Survival in Human Myeloma Cells.

PPAR (Peroxisome proliferator-activated receptor) ß is ubiquitously expressed in all cells and considered to be involved in the lipid metabolism and regulating the inflammatory response and cell proliferation. However, it remain to be clarified the role of PPARß in human myeloma cells. In order to identify the possible ligands for PPARß, we constructed the PPARß response element (PPREß)-lusiferase reporter gene and performed the reporter assay in Hela cell. We found that adrenal cortex hormones (DHEA and DHEA-S etc), dexamethasone (Dex) and baicalein augmented the expression of reporter gene. As already reported by us, baicalein, one of the major flavonoids in Scutellaria baicalensis (Chinese Skullcap), has the suppressive effects on cell proliferation and angiogenesis. Furthermore, baicalein as well as Dex upregulated the expression of PPARß target genes such as ILK and PPARg in myeloma cell lines. Moreover the combination of baicalein with Dex showed cooperative effect on the growth suppression in primary myeloma cells as well as myeloma cell lines. The expression of NF-kB target genes such as IL-6 was also markedly suppressed with the treatment with baiacalein and Dex in U266 cells. Since U266 cells constitutively express RelA(p65), RelB and p50 in the nucleus, we examined whether ligand (baicalein or Dex)-stimulated PPAR ß interacted with RelA in the nucleus of U266 cells or not. We detected physical interaction of PPARß with RelA in the nuclear fraction of U266 cells after stimulation with baicalein or Dex, and also confirmed that baicalein and Dex suppressed the DNA binding of RelA to kB site in the p65 ELISA. Therefore, these data suggest that baicalein combined with Dex can stimulate PPARß-mediated growth suppression in myeloma cells possibly through nuclear interaction between PPARß and RelA (NF-kB) more effectively.