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PPARβ-mediated growth suppression of baicalein and dexamethasone in human myeloma cells

Leukemia volume 21, pages 187–190 (2007)Cite this article

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are originally reported to regulate the expression of genes involved in fatty acid uptake and oxidation, lipid metabolism and inflammation.1 The PPARs consist of three subtypes, PPARα, PPARβ/δ (PPARβ) and PPARγ; PPARα is expressed primarily in the liver, brown adipose tissue, kidney, heart and skeletal muscle, PPARγ is expressed mainly in white and brown adipose tissue, and PPARβ is ubiquitously expressed; PPAR(s) have recently been reported to be involved in tumorigenicity.2 As for the inflammation, PPARs are considered to be anti-inflammatory, and PPAR agonists induce the downregulation of nuclear factor-kappa B (NF-κB) activity. As the constitutive higher activation of NF-κB is considered to be important for the survival and proliferation in B-cell malignancies, including multiple myeloma (MM), it has been extensively explored as to which compounds can inhibit NF-κB activity in the MM.3

The ligand-induced activation of PPARβ is reported to suppress the NF-κB activity. Two possible mechanisms for its downregulation of NF-κB activity were reported: one was the upregulation of IkB gene expression7 and the other was the inhibitory physical interaction between the p65 subunit of NF-κB and PPAR in the nucleus.8 We examined whether PPARβ interacted with the p65 of NF-κB after IL-1α stimulation by the immunoprecipitation followed by Western blotting. Costimulation of IL-1α with Dex and baicalein strongly enhanced the physical interaction between p65 of NF-κB and PPARβ (data not shown). The binding activity of NF-κB (p65/p50) to the κB site was also suppressed in the treatment with Dex and baicalein. Furthermore, the expression of the NF-κB target genes, such as IL-6 and IkBα, was markedly reduced by the treatment of Dex and baicalein combined with IL-1α stimulation in U266 cells.

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Acknowledgements

This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan, the Ministry of Health, Labour and Welfare of Japan; and S Abroun is a recipient of the Postdoctoral Fellowship Award for Foreign Researchers (PO4500) from JSPS.

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Authors and Affiliations

  1. Department of Bio-Signal Analysis, Laboratory of Cellular Signal Analysis, Applied Medical Engineering Science Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan

    K-I Otsuyama, Z Ma, S Abroun, J Amin, K Shamsasenjan & M M Kawano

  2. 4th Department of Internal Medicine, Hiroshima Red Cross Hospital Hiroshima, Hiroshima, Japan

    H Asaoku

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  1. K-I Otsuyama
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Correspondence to M M Kawano.

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Otsuyama, KI., Ma, Z., Abroun, S. et al. PPARβ-mediated growth suppression of baicalein and dexamethasone in human myeloma cells. Leukemia 21, 187–190 (2007). https://doi.org/10.1038/sj.leu.2404462

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