Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress

Autor(es)

Godoy, Paulo R. D. V. ^{[1, 2]} ; Pour Khavari, Ali ^[2] ; Rizzo, Marzia ^[2] ; Sakamoto-Hojo, Elza T. ^{[1, 3]} ; Haghdoost, Siamak ^{[2, 4, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Dept Biol, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Stockholm Univ, Dept Mol Biosci, Wenner Gren Inst, Svante Arrhenius Vag 20C, S-10691 Stockholm - Sweden

^[3] Fac Med Ribeirao Preto, Dept Genet, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Caen Normandy, UMR6252 CIMAP LARIA Team, F-14076 Caen - France

^[5] Adv Resource Ctr HADrontherapy Europe ARCHADE, F-14000 Caen - France

• Tipo de documento: Artigo Científico
• Fonte: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY; v. 2020, JUN 16 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 16/16163-4 - Sensibilização de células tronco do glioma ao dano oxidativo induzido por radiação através do silenciamento de enzimas do sistema antioxidante.
• Beneficiário: Paulo Roberto D'Auria Vieira de Godoy
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado