KU60019, a promising ATM inhibitor sensitizes MCF-7 breast cancer cells to ionizing radiation

Document Type : Original Paper

Authors

1 1-Radiation Biology Research Center, Iran University of Medical Science (IUMS), Tehran, Iran 2-Radiation Science Department, Iran University of Medical Science (IUMS), Tehran, Iran

2 1 Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran 2 Department of Radiation Sciences, School of Para medicine, Iran University of Medical Sciences, Tehran, Iran

3 Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran

10.22038/ijmp.2022.62916.2065

Abstract

Introduction: KU60019 is a selective inhibitor of Ataxia-Telangiectasia Mutated (ATM) kinase which is crucial for cell cycle checkpoints and DNA repair. This study was conducted to examine the radiosensitizing potential of KU60019 against MCF-7 breast cancer cells.

Methods: Cells were treated with different concentrations of KU60019 for 24 h and then irradiated with 6 MV X-ray at doses of 2 and 4 Gy. Finally, the survival rates and apoptosis of the cells in treatment and control groups were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry assays.

Results: The results of the MTT assay showed a higher reduction in the survival rate of cells treated with KU60019 in a dose-dependent manner. Using of KU60019 integration with irradiation substantially increased cell death in comparison to the absence of X-ray. The survival rate of cells treated with 8 µM KU60019 followed by irradiation at the dose of 2 and 4 Gy decreased to the extent of 35% and 51.37% compared to the cells irradiated at the dose of 2 and 4 Gy , respectively. Apoptosis in cells treated with KU60019, followed by irradiation was markedly increased as compared with cells treated with KU60019 alone. Flow cytometry showed, the degree of cell death in cells irradiated at the dose of 4 Gy was increased from 26.40% to 65.90% and 73% when the cells were treated with 4 and 8 µM KU60019, respectively. Our findings demonstrated a high potential of the combination of KU60019 and irradiation in the decrease of survival rate, as well as the increase of apoptosis induction in breast cancer cells.

Conclusion: Hence, KU60019 could be employed as a complementary therapy for women patients with cancers who underwent radiotherapy. Not only could this therapeutic strategy diminish the required dose of irradiation, but the side effects of radiotherapy would be less.

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Articles in Press, Accepted Manuscript
Available Online from 24 April 2022
  • Receive Date: 12 January 2022
  • Revise Date: 16 April 2022
  • Accept Date: 24 April 2022
  • First Publish Date: 24 April 2022