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The Flavonoid Apigenin Suppresses Vitamin D Receptor Expression and Vitamin D Responsiveness in Normal Human Keratinocytes

2000; Elsevier BV; Volume: 268; Issue: 1 Linguagem: Inglês

10.1006/bbrc.2000.2099

1090-2104

Siegfried Segaert, Stéphane Courtois, Marjan Garmyn, H. Degreef, Roger Bouillon,

Vitamin D Research Studies

Apigenin, a flavonoid with chemopreventive properties, induces cellular growth arrest, with concomitant inhibition of intracellular signaling cascades and decreased proto-oncogene expression. We report that apigenin potently inhibited vitamin D receptor (VDR) mRNA and protein expression in human keratinocytes without changes in VDR mRNA half-life. Concurrently, downregulation of retinoid X receptor α, a dramatic loss of c-myc mRNA, and upregulation of p21WAF1 took place. Furthermore, a nearly complete suppression of vitamin D responsiveness was observed as estimated by induction of 24-hydroxylase mRNA. The apigenin effect on VDR expression was shared by some other (quercetine and fisetine) but not all tested flavonoids. Interestingly, the apigenin-mediated VDR suppression was counteracted by the NFκB inhibitors sodium salicylate and caffeic acid phenethyl ester. The presented results propose suppression of nuclear receptor levels as a novel mechanism whereby flavonoids exert their pleiotropic effects. This study may also contribute to the understanding of the regulation of VDR expression in epidermal keratinocytes.