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Targeting NRF2, Reg...
Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress
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- D. V. Godoy, Paulo R. (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,University of São Paulo, Brazil
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- Pour Khavari, Ali (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Rizzo, Marzia (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Sakamoto-Hojo, Elza T. (author)
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- Haghdoost, Siamak (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,University of Caen Normandy, France; Advanced Resource Center for HADrontherapy in Europe (ARCHADE), France
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(creator_code:org_t)
- Hindawi Limited, 2020
- 2020
- English.
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In: Oxidative Medicine and Cellular Longevity. - : Hindawi Limited. - 1942-0900 .- 1942-0994. ; 2020
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Abstract
Subject headings
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- The presence of glioma stem cells (GSCs), which are enriched in neurospheres, may be connected to the radioresistance of glioblastoma (GBM) due to their enhanced antioxidant defense and elevated DNA repair capacity. The aim was to evaluate the responses to different radiation qualities and to reduce radioresistance of U87MG cells, a GBM cell line. U87MG cells were cultured in a 3D model and irradiated with low (24 mGy/h) and high (0.39 Gy/min) dose rates of low LET gamma and high LET carbon ions (1-2 Gy/min). Thereafter, expression of proteins related to oxidative stress response, extracellular 8-oxo-dG, and neurospheres were determined. LD50 for carbon ions was significantly lower compared to LD50 of high and low dose rate gamma radiation. A significantly higher level of 8-oxo-dG was detected in the media of cells exposed to a low dose rate as compared to a high dose rate of gamma or carbon ions. A downregulation of oxidative stress proteins was also observed (NRF2, hMTH1, and SOD1). The NRF2 gene was knocked down by CRISPR/Cas9 in neurosphere cells, resulting in less self-renewal, more differentiated cells, and less proliferation capacity after irradiation with low and high dose rate gamma rays. Overall, U87MG glioma neurospheres presented differential responses to distinct radiation qualities and NRF2 plays an important role in cellular sensitivity to radiation.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- Stem cells
- glioblastoma (GBM)
- radiation
- carbon ions
- gamma radiation
- molekylär biovetenskap
- Molecular Bioscience
Publication and Content Type
- ref (subject category)
- art (subject category)
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