title: Sulforaphane suppresses LPS-induced or TPA-induced downregulation of PDCD4 in RAW 264.7 cells.
abstract: 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.
authors.affiliation: College of Pharmacy, Dongguk University, 814-9 Siksa-dong, Goyang, Gyeonggi-do, 410-820, Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Cho
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Keum
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D013454:Sulfoxides; D013755:Tetradecanoylphorbol Acetate
chemical_list: D051017:Apoptosis Regulatory Proteins; D017879:Isothiocyanates; D008070:Lipopolysaccharides; C498443:Pdcd4 protein, mouse; D016601:RNA-Binding Proteins; D013454:Sulfoxides; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; C016766:sulforaphane; D013755:Tetradecanoylphorbol Acetate
keywords: PDCD4; proteolysis; sulforaphane; transcription