CADD-28. MELATONIN: TARGETING THE CELL'S POWERHOUSE TO FIGHT GLIOBLASTOMA. (5th November 2018)

• Record Type: Journal Article
• Authors: Fernandez-Gil, Beatriz I; Schiappareli, Paula; Vazquez-Ramos, Carla; Sarabia-Estrada, Rachel; Escames, Germaine; Quiñones-Hinojosa, Alfredo
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi280
• Page End: vi281
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.1169
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Mitochondria are the key organelles that control the metabolic state of tumor cells. In particular, mitochondria regulate the Warburg effect, which is one of the main drivers of tumoral behaviour including stemness and resistance to chemotherapy. In previous studies, melatonin has shown to have oncostatic properties when used alone or in combination with chemo-radiation. These anti-cancer properties are thought to be a consequence of melatonin's effects on the mitochondria. The present study examined the use of high concentrations of melatonin to boost the metabolic switch from anaerobic glycolysis to an oxidative phosphorylation (OXPHOS) state in glioblastoma (GBM) cells. Treatment of GBM cells with 3mM melatonin showed a significant decrease in viability (MTT p <0.001) and proliferation (Ki67/DAPI ratio <0.001, RQ PCNA <0.001) after 48 hours. In addition, a significant rise in the reactive oxygen species production (p<0.001) was found. This phenomenon could be explained by an increase in the OXPHOS, inferred from the decrease in the lactate production (p<0.005) and the expression of pyruvate dehydrogenase kinase. The expression of stemness and differentiation genes was also evaluated. We found a significant increase in neural and oligodendrocytes differentiation markers (p<0.005 and p<0.05 respectively) after 7 days of treatment. Finally, we found that melatonin treatment reduced GBM migration capacity (p<0.005) and reduced matrix metalloproteinases expression. In summary, this study reveals that melatonin can force a metabolic switch inducing cell differentiation, eventually leading to a decrease in the malignant properties of GBM cells in vitro. Our findings highlight melatonin as a relevant therapeutic approach to target GBM by modulating cell metabolism.