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Sulforaphane Suppresses LPS‐Induced or TPA‐Induced Downregulation of PDCD4 in RAW 264.7 Cells
Author(s) -
Cho JongHo,
Kim YoungWoo,
Keum YoungSam
Publication year - 2014
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5171
Subject(s) - sulforaphane , downregulation and upregulation , cruciferous vegetables , isothiocyanate , microbiology and biotechnology , chemistry , p70 s6 kinase 1 , lipopolysaccharide , biochemistry , phosphorylation , biology , immunology , protein kinase b , cancer , genetics , gene
Sulforaphane is a natural chemopreventive isothiocyanate and abundantly found in various cruciferous vegetables. Although chemopreventive activity of sulforaphane is well documented, the detailed biochemical mechanism(s), underlying how it regulates the protein translation process to antagonize pro‐inflammatory responses are largely unclear. In the present study, we show that lipopolysaccharide (LPS) or 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) treatment reduces cellular levels of PDCD4, and this event is mediated by affecting both transcription and proteolysis in RAW 264.7 cells. We show that LPS‐mediated or TPA‐mediated PDCD4 downregulation is catalyzed by the activation of intracellular Akt1 or S6K1 kinases and that sulforaphane suppresses LPS‐induced or TPA‐induced Akt1 or S6K1 activation, thereby resulting in the attenuation of PDCD4 downregulation in RAW 264.7 cells. We propose that sulforaphane suppression of PDCD4 downregulation serves as a novel molecular mechanism to control proliferation in response to pro‐inflammatory signals. Copyright © 2014 John Wiley & Sons, Ltd.