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

Most cancer cells, including GL15 glioblastomacells, rely on glycolysis for energy supply. The effect ofantiglycolytic bromopyruvate on respiratory parameters andviability of GL15 cells was investigated. Bromopyruvatecaused Δψm and MTT collapse, ATP decrease, and cellviability loss without involving apoptotic or necrotic pathways.The autophagy marker LC3-II was increased. Δψmdecrease was accompanied by reactive oxygen species(ROS) increase and cytochrome c (cyt c) disappearance,suggesting a link between free radical generation andintramitochondrial cyt c degradation. Indeed, the freeradical inducer menadione caused a decrease in cyt c thatwas reversed by N-acetylcysteine. Cyt c is tightly bound tothe inner mitochondrial membrane in GL15 cells, whichmay confer protein peroxidase activity, resulting in autooxidationand protein targeting to degradation in thepresence of ROS. This process is directed towardsimpairment of the apoptotic cyt c cascade, although cellsare committed to die.