title: Flavonoids suppress human glioblastoma cell growth by inhibiting cell metabolism, migration, and by regulating extracellular matrix proteins and metalloproteinases expression.
abstract: The malignant gliomas are very common primary brain tumors with poor prognosis, which require more effective therapies than the current used, such as with chemotherapy drugs. In this work, we investigated the effects of several polyhydroxylated flavonoids namely, rutin, quercetin (F7), apigenin (F32), chrysin (F11), kaempferol (F12), and 3',4'-dihydroxyflavone (F2) in human GL-15 glioblastoma cells. We observed that all flavonoids decreased the number of viable cells and the mitochondrial metabolism. Furthermore, they damaged mitochondria and rough endoplasmic reticulum, inducing apoptosis. Flavonoids also induced a delay in cell migration, related to a reduction in filopodia-like structures on the cell surface, reduction on metalloproteinase (MMP-2) expression and activity, as well as an increase in intra- and extracellular expression of fibronectin, and intracellular expression of laminin. Morphological changes were also evident in adherent cells characterized by the presence of a condensed cell body with thin and long cellular processes, expressing glial fibrillary acidic protein (GFAP). Therefore, these flavonoids should be tested as potential antitumor agents in vitro and in vivo in other malignant glioma models.
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Balbino L
authors.initials: BL
authors.lastname: Santos
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Mona N
authors.initials: MN
authors.lastname: Oliveira
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Paulo L C
authors.initials: PL
authors.lastname: Coelho
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Bruno P S
authors.initials: BP
authors.lastname: Pitanga
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Alessandra B
authors.initials: AB
authors.lastname: da Silva
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Taís
authors.initials: T
authors.lastname: Adelita
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Victor Diógenes A
authors.initials: VD
authors.lastname: Silva
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Maria de F D
authors.initials: Mde F
authors.lastname: Costa
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Ramon S
authors.initials: RS
authors.lastname: El-Bachá
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil.
authors.forename: Marcienne
authors.initials: M
authors.lastname: Tardy
authors.affiliation: Neuroscience Paris Seine INSERM U 1130, CNRS UMR 8246, UPMC UM CR18, Université Pierre et Marie Curie, Campus Jussieu, 9 Quai Saint-Bernard, Batiments A-B, 75005, Paris.
authors.forename: Hervé
authors.initials: H
authors.lastname: Chneiweiss
authors.affiliation: Neuroscience Paris Seine INSERM U 1130, CNRS UMR 8246, UPMC UM CR18, Université Pierre et Marie Curie, Campus Jussieu, 9 Quai Saint-Bernard, Batiments A-B, 75005, Paris.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Junier
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, CCS - Bloco F, 21949-590, Rio de Janeiro, Brazil.
authors.forename: Vivaldo
authors.initials: V
authors.lastname: Moura-Neto
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Av. Reitor Miguel Calmon s/n, Vale do Canela, 40110-902, Salvador, BA, Brazil. Electronic address: costasl@ufba.br.
authors.forename: Silvia L
authors.initials: SL
authors.lastname: Costa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016326:Extracellular Matrix Proteins; D005419:Flavonoids; D045726:Metalloproteases
keywords: Differentiation; Fibronectin; Flavonoids; Glioblastoma; Invasion; Metalloproteinase