Dexamethasone acts as a radiosensitizer in three astrocytoma cell lines via oxidative stress
| Autor: | Sylvia Ortega-Martínez |
|---|---|
| Přispěvatelé: | Ministerio de Educación y Cultura (España), University of Washington, Oxford University Museum of Natural History, Ministerio de Ciencia e Innovación (España) |
| Rok vydání: | 2015 |
| Předmět: |
Pathology
Radiation-Sensitizing Agents DNA Repair Clinical Biochemistry GCs glucocorticoids Apoptosis medicine.disease_cause DNA damage response Biochemistry Dexamethasone Histones Radiation Ionizing Medicine DEXA dexamethasone lcsh:QH301-705.5 lcsh:R5-920 Intracellular Signaling Peptides and Proteins Cell cycle musculoskeletal system DDR DNA Damage response Comet Assay lcsh:Medicine (General) Tumor Suppressor p53-Binding Protein 1 Research Paper musculoskeletal diseases Programmed cell death Radiosensitizer medicine.medical_specialty DNA repair DNA damage MR mineralocorticoid receptor Astrocytoma Time-Lapse Imaging Cell Line Tumor IR Irradiation Humans Radiosensitivity Glucocorticoids GR glucocorticoid receptor business.industry Organic Chemistry Cell Cycle Checkpoints Ascorbic acid NHEJ non-homologous end-joining pathway Oxidative Stress lcsh:Biology (General) Microscopy Fluorescence DSBs double strand breaks Cancer research business Oxidative stress Astrocytomas |
| Zdroj: | Redox Biology Redox Biology, Vol 5, Iss, Pp 388-397 (2015) Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2213-2317 |
| DOI: | 10.1016/j.redox.2015.06.006 |
| Popis: | 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 4 h 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 2 h 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. Graphical abstract Highlights ● Dexamethasone causes DNA damage by increasing gamma-H2AX levels in three astrocytoma cell lines (CT2A, APP.PS1 L.1 and APP.PS1 L.3) ● Dexamethasone affects DNA repair kinetics and produces cell death in three astrocytoma cell lines (CT2A, APP.PS1 L.1 and APP.PS1 L.3) even dexamethasone does not affect any cell cycle arrest in any cell line studied. ● Oxidative stress appears to be one of the mechanisms of dexamethasone action in DNA damage as their effect is reversed with ascorbic acid addition. |
| Databáze: | OpenAIRE |
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