Mahdi Abbasian1,2, Azam Baharlouei2,3, Zahra Arab-Bafrani4,5,6, David A Lightfoot7. 1. Stem Cell Research Center, Golestan University of Medical Science, Gorgān, Iran. 2. Department of Biotechnology, College of Agriculture, Isfahan University of Technology, Isfahan, Iran. 3. Department of Microbiology, Southern Illinois University at Carbondale, Carbondale, IL, 62901, USA. 4. Stem Cell Research Center, Golestan University of Medical Science, Gorgān, Iran. arabbafrani@goums.ac.ir. 5. Department of Biochemistry and Biophysics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgān, Iran. arabbafrani@goums.ac.ir. 6. Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgān, Iran. arabbafrani@goums.ac.ir. 7. Department of Plant, Soil and Agricultural Systems, Plant Biotechnology and Genome Core-Facility, Southern Illinois University at Carbondale, Carbondale, IL, 62901, USA.
Abstract
PURPOSE: High-linear energy transfer (high LET) irradiation has significant cytotoxic effects on different cancerous stem-like cells (CSLCs) such as colorectal CSLCs. A review of the literature has indicated that the presence of gold nanoparticles (GNPs) enables low-LET irradiation to produce highly non-homogeneous dose distributions like high-LET irradiation. The purpose of this study was to evaluate the radioresponsiveness of HT29 colorectal CSLCs under low-LET irradiation (X-ray) and in the presence of GNPs. METHODS: Radioresponsiveness was evaluated using the ϒ-H2AX foci formation assay, the clonogenic assay, the cell cycle progression assay and analyses of radiobiological parameters. RESULTS: In the presence of GNPs, the survival fraction of HT29 CSLCs was significantly reduced and caused significant changes in the radiobiological parameters after irradiation. In addition, ϒ-H2AX assay showed that in the presence of GNPs, the persistent DNA double-strand breaks were significantly increased in irradiated HT29 CSLCs. The relative biological effectiveness value of GNPs with X-rays was about 1.6 for HT-29 CSLCs at the 10% of cell survival fraction (D10 level) when compared to X-rays alone. CONCLUSION: Therefore, the combination of GNPs with X-ray irradiation has the potential to kill HT29 CSLCs greater than the X-ray alone, and may be considered as an alternative for high-LET irradiation.
PURPOSE: High-linear energy transfer (high LET) irradiation has significant cytotoxic effects on different cancerous stem-like cells (CSLCs) such as colorectal CSLCs. A review of the literature has indicated that the presence of gold nanoparticles (GNPs) enables low-LET irradiation to produce highly non-homogeneous dose distributions like high-LET irradiation. The purpose of this study was to evaluate the radioresponsiveness of HT29 colorectal CSLCs under low-LET irradiation (X-ray) and in the presence of GNPs. METHODS: Radioresponsiveness was evaluated using the ϒ-H2AX foci formation assay, the clonogenic assay, the cell cycle progression assay and analyses of radiobiological parameters. RESULTS: In the presence of GNPs, the survival fraction of HT29 CSLCs was significantly reduced and caused significant changes in the radiobiological parameters after irradiation. In addition, ϒ-H2AX assay showed that in the presence of GNPs, the persistent DNA double-strand breaks were significantly increased in irradiated HT29 CSLCs. The relative biological effectiveness value of GNPs with X-rays was about 1.6 for HT-29 CSLCs at the 10% of cell survival fraction (D10 level) when compared to X-rays alone. CONCLUSION: Therefore, the combination of GNPs with X-ray irradiation has the potential to kill HT29 CSLCs greater than the X-ray alone, and may be considered as an alternative for high-LET irradiation.
Entities:
Keywords:
Cancer stem-like cell; DNA DSBs; Gold nanoparticle; RBE value
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