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Sodium sulfide selectively induces oxidative stress, DNA damage, and mitochondrial dysfunction and radiosensitizes glioblastoma (GBM) cells.
Xiao, Adam Y; Maynard, Matthew R; Piett, Cortt G; Nagel, Zachary D; Alexander, J Steven; Kevil, Christopher G; Berridge, Michael V; Pattillo, Christopher B; Rosen, Lane R; Miriyala, Sumitra; Harrison, Lynn.
Afiliación
  • Xiao AY; Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
  • Maynard MR; Radiation Oncology, Willis-Knighton Cancer Center, Shreveport, LA, 71103, USA.
  • Piett CG; Harvard University, School of Public Health, Boston, MA, 02115, USA.
  • Nagel ZD; Harvard University, School of Public Health, Boston, MA, 02115, USA.
  • Alexander JS; Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
  • Kevil CG; Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
  • Berridge MV; Malaghan Institute of Medical Research, Wellington, 6242, New Zealand.
  • Pattillo CB; Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
  • Rosen LR; Radiation Oncology, Willis-Knighton Cancer Center, Shreveport, LA, 71103, USA.
  • Miriyala S; Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
  • Harrison L; Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA. Electronic address: lclary@lsuhsc.edu.
Redox Biol ; 26: 101220, 2019 09.
Article en En | MEDLINE | ID: mdl-31176262
Glioblastoma (GBM) has a poor prognosis despite intensive treatment with surgery and chemoradiotherapy. Previous studies using dose-escalated radiotherapy have demonstrated improved survival; however, increased rates of radionecrosis have limited its use. Development of radiosensitizers could improve patient outcome. In the present study, we report the use of sodium sulfide (Na2S), a hydrogen sulfide (H2S) donor, to selectively kill GBM cells (T98G and U87) while sparing normal human cerebral microvascular endothelial cells (hCMEC/D3). Na2S also decreased mitochondrial respiration, increased oxidative stress and induced γH2AX foci and oxidative base damage in GBM cells. Since Na2S did not significantly alter T98G capacity to perform non-homologous end-joining or base excision repair, it is possible that GBM cell killing could be attributed to increased damage induction due to enhanced reactive oxygen species production. Interestingly, Na2S enhanced mitochondrial respiration, produced a more reducing environment and did not induce high levels of DNA damage in hCMEC/D3. Taken together, this data suggests involvement of mitochondrial respiration in Na2S toxicity in GBM cells. The fact that survival of LN-18 GBM cells lacking mitochondrial DNA (ρ0) was not altered by Na2S whereas the survival of LN-18 ρ+ cells was compromised supports this conclusion. When cells were treated with Na2S and photon or proton radiation, GBM cell killing was enhanced, which opens the possibility of H2S being a radiosensitizer. Therefore, this study provides the first evidence that H2S donors could be used in GBM therapy to potentiate radiation-induced killing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Sensibilizantes a Radiaciones / Sulfuros / Neuroglía / Reparación del ADN / Sulfuro de Hidrógeno / Mitocondrias Límite: Humans Idioma: En Revista: Redox Biol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Sensibilizantes a Radiaciones / Sulfuros / Neuroglía / Reparación del ADN / Sulfuro de Hidrógeno / Mitocondrias Límite: Humans Idioma: En Revista: Redox Biol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos