title: Mitochondrial dysfunction and effect of antiglycolytic bromopyruvic acid in GL15 glioblastoma cells.
abstract: Most cancer cells, including GL15 glioblastoma cells, rely on glycolysis for energy supply. The effect of antiglycolytic bromopyruvate on respiratory parameters and viability of GL15 cells was investigated. Bromopyruvate caused Δψ(m) and MTT collapse, ATP decrease, and cell viability loss without involving apoptotic or necrotic pathways. The autophagy marker LC3-II was increased. Δψ(m) decrease was accompanied by reactive oxygen species (ROS) increase and cytochrome c (cyt c) disappearance, suggesting a link between free radical generation and intramitochondrial cyt c degradation. Indeed, the free radical inducer menadione caused a decrease in cyt c that was reversed by N-acetylcysteine. Cyt c is tightly bound to the inner mitochondrial membrane in GL15 cells, which may confer protein peroxidase activity, resulting in auto-oxidation and protein targeting to degradation in the presence of ROS. This process is directed towards impairment of the apoptotic cyt c cascade, although cells are committed to die.
authors.affiliation: Department of Internal Medicine, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Macchioni
authors.forename: Magdalena
authors.initials: M
authors.lastname: Davidescu
authors.forename: Miriam
authors.initials: M
authors.lastname: Sciaccaluga
authors.forename: Cristina
authors.initials: C
authors.lastname: Marchetti
authors.forename: Graziella
authors.initials: G
authors.lastname: Migliorati
authors.forename: Stefano
authors.initials: S
authors.lastname: Coaccioli
authors.forename: Rita
authors.initials: R
authors.lastname: Roberti
authors.forename: Lanfranco
authors.initials: L
authors.lastname: Corazzi
authors.forename: Emilia
authors.initials: E
authors.lastname: Castigli
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D011773:Pyruvates / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D011773:Pyruvates; D017382:Reactive Oxygen Species; C017092:bromopyruvate; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D000111:Acetylcysteine