Discussion
Chronic exposure to DNP in BMG-1 cells resulted in dual-state hyper-energy metabolism with elevated glycolysis++ and OXPHOS++ compared to parental BMG-1 cells with low glycolysis+ and OXPHOS+. Tumor xenograft of OPM-BMG cells showed relatively increased tumor-forming potential and accelerated tumor growth in nude mice. Moreover, compared to BMG-1, OPM-BMG tumor-derived cells also showed enhanced migration and invasion potential. Although mitochondrial uncouplers are proposed as a valuable anti-cancer strategy; however, our findings reveal that prolonged exposure to uncouplers provides tumor growth advantage over the existing glioma phenotype that may lead to poor clinical outcomes.
Methods
BMG-1 cells were treated with 2,4-dinitrophenol (DNP) in-vitro, to establish the OXPHOS-modified (OPM-BMG) cells. Further cellular metabolic characterization was carried out in both in-vitro cellular model and in-vivo tumor xenografts to dissect the role of metabolic adaptation in these cells and compared them with their parental phenotype.