Mechanistic studies showed that 12 induced ROS-dependent and autophagy-independent death of glioblastoma cells associated with mitochondrial stress, probably driven by direct interaction of 12 with the active site of mitochondrial LonP1 protease, which led to the dissipation of ΔψM, abundant ROS generation and mitogenesis, with subsequent activation of caspase-mediated apoptosis. This evidence concerns the gene LONP1 and glioblastoma.