Kaempferol inhibits cell transformation by suppressing RSK2/histone H3 signaling

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The ribosomal S6 kinase 2 (RSK2), a member of the p90^RSK (RSK) family of proteins, is a widely expressed serine/threonine kinase that is activated by ERK1/2 and PDK1 in response to many growth factors and peptide hormones. Activation of RSK2 signaling enhances cell survival. We found that kaemperol, a natural chemical compound abundant in many foods, specifically inhibited RSK2 activity in vitro and in vivo. Furthermore, kaemperol suppressed tumor promoter-induced cell transformation of JB6 Cl41 cells as determined by a soft agar assay. RSK2 overexpression induced cell proliferation and anchorage-independent cell transformation, and knockdown or knockout of RSK2 suppressed cell proliferation and foci formation compared with wildtype control cells. The mechanism was associated with impairment of the G1/S cell cycle transition. Furthermore, kaemperol-mediated RSK2 inhibition suppressed tumor promoter-induced histone H3 phosphorylation at serine 10 and RSK2 knockdown or deficiency also decreased EGF-induced histone H3 phosphorylation at serine 10. These results provide evidence that kaemperol is a potential chemopreventive compound that can effectively suppresss RSK2 activity.