title: Carbazolequinone induction of caspase-dependent cell death in Src-overexpressing cells.
abstract: We previously reported that RSV-transformed quail neuroretina cells (QNR-ts68) were highly resistant to apoptosis provoked by serum withdrawal, and that this property was due to v-Src kinase activity. The present study investigates the cytotoxic effect and the functional mechanism of carbazolequinone-mediated cell death in this system. QNR-ts68 cells were subjected to carbazolequinone treatment and both growth inhibition and cell death induction were examined using formazan assays. Cell death mechanism (both apoptosis and necrosis) was confirmed through phosphatidyl serine exposure and propidium iodide incorporation. Furthermore, the effect of active carbazolequinone was inhibited by a pan caspase inhibitor. Cytofluorimetric and immunofluorescence data demonstrated the activation of caspase-3 and the involvement of mitochondria. Therefore, this study clearly indicates that carbazolequinones could induce cell death in transformed cells displaying high levels of antiapoptotic tyrosine kinase activity. Further investigations would be necessary to elucidate the mechanisms by which these carbazolequinones act as antitumor agents.
authors.affiliation: Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS/Université Claude Bernard, 7 passage du Vercors, F69367, Lyon, France.
authors.forename: Abdel
authors.initials: A
authors.lastname: Aouacheria
authors.forename: Benjamin
authors.initials: B
authors.lastname: Néel
authors.forename: Zouhair
authors.initials: Z
authors.lastname: Bouaziz
authors.forename: Rigal
authors.initials: R
authors.lastname: Dominique
authors.forename: Nadia
authors.initials: N
authors.lastname: Walchshofer
authors.forename: Joëlle
authors.initials: J
authors.lastname: Paris
authors.forename: Houda
authors.initials: H
authors.lastname: Fillion
authors.forename: Germain
authors.initials: G
authors.lastname: Gillet
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000502:physiology; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D004347:Drug Interactions; D004789:Enzyme Activation; D007473:Ion Channels / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009336:Necrosis; D011784:Quail; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014157:Transcription Factors
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D001426:Bacterial Proteins; D002227:Carbazoles; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011809:Quinones; D014157:Transcription Factors; C092195:VsrC protein, Ralstonia solanacearum; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D020169:Caspases