title: Phosphoprotein levels, MAPK activities and NFkappaB expression are affected by fisetin.
abstract: Flavonoids, polyphenolic phytochemicals, are ubiquitous in plants and are commonly present in the human diet. They may exert diverse beneficial effects, including antioxidant and anticarcinogenic activities. The present study was designed to evaluate three biomolecules that play important roles in the apoptotic process: mitogen-activated protein kinases, protein phosphatases and NFkappaB, using HL60 cells treated with fisetin as an experimental model. Our results demonstrated that cells treated with fisetin presented high expression of NFkappaB, activation of MAPK p38 and an increase of phosphoprotein levels; inhibition of enzymes involved in redox status maintenance were also observed. Our findings reinforce the hypothesis that fisetin is likely to exert beneficial and/or toxic actions on cells not through its potential as antioxidant but rather through its modulation of protein kinase and phosphatase signaling cascades. Additionally, our results also indicate that the cellular effects of fisetin will ultimately depend on the cell type and on the extent to which they associate with the cells, either by interactions at the membrane or by uptake into the cytosol.
authors.affiliation: Department of Biochemistry, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Roberta R Ruela
authors.initials: RR
authors.lastname: de Sousa
authors.forename: Karla Cristiana Souza
authors.initials: KC
authors.lastname: Queiroz
authors.forename: Ana Carolina Santos
authors.initials: AC
authors.lastname: Souza
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Gurgueira
authors.forename: Amanda Cavallari
authors.initials: AC
authors.lastname: Augusto
authors.forename: Marcio André
authors.initials: MA
authors.lastname: Miranda
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.forename: Carmen Veríssima
authors.initials: CV
authors.lastname: Ferreira
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000378:metabolism*; D044948:Flavonols; D018922:HL-60 Cells; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008956:Models, Chemical; D016328:NF-kappa B / Q000096:biosynthesis*; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D044948:Flavonols; D016328:NF-kappa B; D010750:Phosphoproteins; D048051:p38 Mitogen-Activated Protein Kinases; C017875:fisetin