title: Quercetin derivative induces cell death in glioma cells by modulating NF-κB nuclear translocation and caspase-3 activation.
abstract: Treated glioblastoma multiforme (GBM) patients only survive 6 to 14months after diagnosis; therefore, the development of novel therapeutic strategies to treat gliomas remains critically necessary. Considering that phenolic compounds, like quercetin, have the potential to be used in the chemotreatment of gliomas and that some flavonoids exhibit the ability to cross the BBB, in the present study, we investigated the antitumor effect of flavonoids (including chalcones, flavones, flavanones and flavonols). Initially their activities were tested in C6 glioma cells screened using the MTT method, resulting in the selection of chalcone 2 whose feasibility was confirmed by a Trypan Blue exclusion assay in the low μM range on C6 glioma cells. Cell cycle and apoptotic death analyses on C6 glioma cells were also performed, and chalcone 2 increased the apoptosis of the cells but did not alter the cell cycle progression. In addition, treatments with these two compounds were not cytotoxic to hippocampal organotypic cultures, a model of healthy neural cells. Furthermore, the results indicated that 2 induced apoptosis by inhibition of NF-κB and activation of active caspase-3 in glioma cells, suggesting that it is a potential prototype to develop new treatments for GBM in the future.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Cíntia J
authors.initials: CJ
authors.lastname: Kiekow
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ramiro Barcelos, 2600, Anexo, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Fabrício
authors.initials: F
authors.lastname: Figueiró
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ramiro Barcelos, 2600, Anexo, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Fabrícia
authors.initials: F
authors.lastname: Dietrich
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Luciana Dalla
authors.initials: LD
authors.lastname: Vechia
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ramiro Barcelos, 2600, Anexo, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Elisa N S
authors.initials: EN
authors.lastname: Pires
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ramiro Barcelos, 2600, Anexo, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Elisa H F
authors.initials: EH
authors.lastname: Jandrey
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Simone C B
authors.initials: SC
authors.lastname: Gnoatto
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ramiro Barcelos, 2600, Anexo, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Christianne G
authors.initials: CG
authors.lastname: Salbego
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ramiro Barcelos, 2600, Anexo, 90035-003, Porto Alegre, RS, Brazil. Electronic address: abattastini@gmail.com.
authors.forename: Ana Maria O
authors.initials: AM
authors.lastname: Battastini
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 90610-000, Porto Alegre, RS, Brazil. Electronic address: gracegosmann@gmail.com.
authors.forename: Grace
authors.initials: G
authors.lastname: Gosmann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D011794:Quercetin; D053148:Caspase 3
keywords: 2′,4′-Dihydroxy-4-methoxychalcone (PubChem CID: 166795); 3,3′,5,5′-Tetramethoxychalcone (PubChem CID: 51355269); 7-Hydroxy-4′-methoxyflavone (PubChem CID: 5320693); Antitumoral; Apoptosis; Chalcone; Glioma; Morin (PubChem CID: 5281670); NF-κB; Polyphenol; Quercetin (PubChem CID: 5280343)