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Inhibition of ATM kinase upregulates levels of cell death induced by cannabidiol and γ-irradiation in human glioblastoma cells.


ABSTRACT: Despite advances in glioblastoma (GBM) therapy, prognosis of the disease remains poor with a low survival rate. Cannabidiol (CBD) can induce cell death and enhance radiosensitivity of GBM but not normal astrocytes. Inhibition of ATM kinase is an alternative mechanism for radiosensitization of cancer cells. In this study, we increased the cytotoxic effects of the combination of CBD and γ-irradiation in GBM cells through additional inhibition of ATM kinase with KU60019, a small molecule inhibitor of ATM kinase. We observed in GBM cells treated by CBD, γ-irradiation and KU60019 high levels of apoptosis together with strong upregulation of the percentage of G2/M-arrested cells, blockade of cell proliferation and a massive production of pro-inflammatory cytokines. Overall, these changes caused

SUBMITTER: Ivanov VN 

PROVIDER: S-EPMC6368233 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature