Alternative responses of primary tumor cells and glioblastoma cell lines to N,N-bis-(8-hydroxyquinoline-5-yl methyl)-benzyl substituted amines: Cell death versus P53-independent senescence - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue International Journal of Oncology Année : 2010

Alternative responses of primary tumor cells and glioblastoma cell lines to N,N-bis-(8-hydroxyquinoline-5-yl methyl)-benzyl substituted amines: Cell death versus P53-independent senescence

Jean-Louis Kraus
  • Fonction : Auteur
Filippo Conti
  • Fonction : Auteur
Sébastien Madonna
  • Fonction : Auteur
Christophe Beclin
  • Fonction : Auteur

Résumé

N,N-bis-(8-hydroxyquinoline-5-yl methyl)-benzyl substituted amines (HQNBA) represent a new class of compounds showing anti-cancer activity. At the chemical level the compounds were shown to react preferentially with thiol radicals which may lead to unfolded cysteine containing proteins and subsequent ER-stress. At the molecular level, treatment of U87 cells with this class of derivatives induced an over-expression of stress genes, including P53 and numerous P53 target genes. By generating shRNA U87 cell clones impaired in P53 expression we found that P53 mediates neither proliferation arrest of treated U87 cells nor over-expression of potential P53 targets. Moreover, we discovered that a representative HQNBA derivative (JLK1486) induces strong but transient senescence in U87 cells in a P53-independent manner. We demonstrate that, in contrast to its effect on established glioblastoma cell lines, JLK1486 induces extensive death of primary glioblastoma cells. We provide evidence that both caspase 3, and 7 activation, and cathepsin B and D activities account for at least part of this cell death.

Dates et versions

hal-03090060 , version 1 (29-12-2020)

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Citer

Jean-Louis Kraus, Filippo Conti, Sébastien Madonna, Aurelie Tchoghandjian, Christophe Beclin. Alternative responses of primary tumor cells and glioblastoma cell lines to N,N-bis-(8-hydroxyquinoline-5-yl methyl)-benzyl substituted amines: Cell death versus P53-independent senescence. International Journal of Oncology, 2010, 37 (6), pp.1463-70. ⟨10.3892/ijo_00000798⟩. ⟨hal-03090060⟩

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