title: Dexamethasone acts as a radiosensitizer in three astrocytoma cell lines via oxidative stress.
abstract: Glucocorticoids (GCs), which act on stress pathways, are well-established in the co-treatment of different kinds of tumors; however, the underlying mechanisms by which GCs act are not yet well elucidated. As such, this work investigates the role of glucocorticoids, specifically dexamethasone (DEXA), in the processes referred to as DNA damage and DNA damage response (DDR), establishing a new approach in three astrocytomas cell lines (CT2A, APP.PS1 L.1 and APP.PS1 L.3). The results show that DEXA administration increased the basal levels of gamma-H2AX foci, keeping them higher 4h after irradiation (IR) of the cells, compared to untreated cells. This means that DEXA might cause increased radiosensitivity in these cell lines. On the other hand, DEXA did not have an apparent effect on the formation and disappearance of the 53BP1 foci. Furthermore, it was found that DEXA administered 2h before IR led to a radical change in DNA repair kinetics, even DEXA does not affect cell cycle. It is important to highlight that DEXA produced cell death in these cell lines compared to untreated cells. Finally and most important, the high levels of gamma-H2AX could be reversed by administration of ascorbic acid, a potent blocker of reactive oxygen species, suggesting that DEXA acts by causing DNA damage via oxidative stress. These exiting findings suggest that DEXA might promote radiosensitivity in brain tumors, specifically in astrocytoma-like tumors.
authors.affiliation: Molecular, Cellular and Developmental Neurobiology Department, Cajal Institute, CSIC, Madrid, Spain.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Ortega-Martínez
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair; D003907:Dexamethasone / Q000633:toxicity*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D059008:Time-Lapse Imaging; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D011838:Radiation-Sensitizing Agents; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D003907:Dexamethasone
keywords: Astrocytomas; DNA damage; DNA damage response; DNA repair; Dexamethasone; Glucocorticoids