Abstract 1498: Melatonin inhibits mitochondrial transcription factor A expression in glioblastoma U87MG cell culture inducing an anti-tumorigenic effect

Abstract

Abstract Melatonin, the major hormone of pineal gland, has been described to induce intrinsic apoptosis in tumor cell, while it is inhibited in non-tumor cell. In tumor cell, melatonin stimulates intracellular production of reactive oxygen species (ROS) by a mechanism not completely understood. Here we propose that melatonin inhibits the expression of the mitochondrial transcription factor A (TFAM) in culture of glioblastoma (GBM) cell lineage, leading to an increase of the production of ROS. TFAM is an important mitochondrial protein that maintains the mitochondrial DNA (mtDNA) integrity and consequently the oxidative phosphorylation. Human U87MG GBM cell lineage was treated with melatonin (1 mM) for 72 h to evaluate the expression of TFAM and the mtDNA copy number through Real Time PCR. Proliferation, apoptosis, cell cycle and ROS production were also evaluated by cytometry (Muse - Millipore Corporation) and the results were normalized to control (vehicle: ethanol 0.3 %). Melatonin reduced the expression of TFAM in 17.5 % compared to the control group, but had no effect on the mtDNA copy number. Moreover, the incubation of U87MG with melatonin induced a reduction in cell proliferation in 14.24 % ± 4.3 compared to control, with an arrest of cell cycle in G0/G1 phase, which increased from 67.4 ± 3.71 % to 72.78 ± 3.18 % in the group treated with melatonin compared to the control. Production of ROS presented an increase of 7.1 %, with no significant effect on apoptosis. These results suggest that TFAM maybe a target for the melatonin function for an anti-tumorigenic effect through an increase of ROS production, inducing a delay in the cell cycle and a reduction of cell proliferation. The melatonin effect onTFAM maybe a novel signaling pathway that could be explored for the control of GBM progression. Citation Format: Daiane G. Franco, Isabele F. Moretti, Suely K. Marie. Melatonin inhibits mitochondrial transcription factor A expression in glioblastoma U87MG cell culture inducing an anti-tumorigenic effect [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1498. doi:10.1158/1538-7445.AM2017-1498