Mitochondrial dysfunction and effect of antiglycolytic bromopyruvic acid in GL15 glioblastoma cells

• DOI: 10.1007/s10863-011-9375-2
• Publication Date: 2011-07-20T10:39:43Z
• Authors: Lara Macchioni; Magdalena Davidescu; Miriam Sciaccaluga; Cristina Marchetti; Graziella Migliorati; Stefano Coaccioli; Rita Roberti; Lanfranco Corazzi; Emilia Castigli
• Keywords: Membrane Potential, Mitochondrial; 0301 basic medicine; Cytochromes c; Apoptosis; Free Radical Scavengers; Acetylcysteine; Mitochondria; 03 medical and health sciences; Adenosine Triphosphate; GL15 cells, Cytochrome c, ROS, Mitochondrial membrane potential, Bromopyruvate, Respiratory chain inhibitors; Cell Line, Tumor; Mitochondrial Membranes; Proteolysis; Humans; Enzyme Inhibitors; Glioblastoma; Pyruvates; Reactive Oxygen Species; Glycolysis; Oxidation-Reduction

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.