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Inhibition of DNA Double-Strand Break Repair by Niclosamide in Human Colorectal Cancer Cells

  • MATERIALS FROM THE INTERNATIONAL CONFERENCE “RADIATION EXPOSURE-RELATED PROBLEMS OF CHEMICAL PROTECTION AND REPAIR” (DUBNA, 30–31 MAY, 2018)
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Abstract

The radiosensitizing effect of niclosamide against human rectal adenocarcinoma cells SW837 and human sigmoid colon carcinoma cells COLO 320 HSR and the underlying molecular mechanisms were investigated in this study. The survival rate of tumor cells under treatment with niclosamide, γ-radiation, and their combination was evaluated. The level of MDR1, Bcl-2, β-catenin, and γH2AX histone, a marker of DNA double-strand breaks (DSBs), was determined by flow cytometry using immunocytochemical methods. It was shown that the combined treatment with niclosamide and γ-radiation led to more intense tumor cell death than when niclosamide and γ-radiation were used separately. A decrease in the level of β-catenin was detected in the cells of the COLO 320 HSR line under treatment with niclosamide, which was more intense under combined treatment with niclosamide and irradiation. At the same time, the content of β-catenin in the cells of the SW837 line remained unchanged under treatment with niclosamide and γ-radiation and under their combined use. Niclosamide did not lead to the formation of DNA DSBs in unirradiated cells and did not increase their level 1 h after radiation exposure. The treatment of the cells with niclosamide before irradiation led to the fact that 24 h after irradiation the level of γH2AX histone, reflecting the number of DNA DSBs, was 1.6 times higher than that in intact cells and the cells exposed only to radiation. This evidences the inhibition of DNA DSB repair induced by γ-radiation. Thus, niclosamide possesses a radiosensitizing effect on human colorectal cancer cells, which is based on inhibition of DNA DSB repair. The inhibition of the Wnt/β-catenin signaling pathway under treatment with niclosamide is not detected in all types of tumor cells.

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Authors and Affiliations

  1. National Research Centre “Kurchatov Institute, Moscow, Russia

    A. S. Zhirnik, Y. P. Semochkina & E. Yu. Moskaleva

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  1. A. S. Zhirnik
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  2. Y. P. Semochkina
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  3. E. Yu. Moskaleva
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Correspondence to A. S. Zhirnik.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by D. Novikova

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Zhirnik, A.S., Semochkina, Y.P. & Moskaleva, E.Y. Inhibition of DNA Double-Strand Break Repair by Niclosamide in Human Colorectal Cancer Cells. Biol Bull Russ Acad Sci 46, 1633–1640 (2019). https://doi.org/10.1134/S1062359019120100

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