Combination of gold nanoparticles with low-LET irradiation: an approach to enhance DNA DSB induction in HT29 colorectal cancer stem-like cells

J Cancer Res Clin Oncol. 2019 Jan;145(1):97-107. doi: 10.1007/s00432-018-2769-3. Epub 2018 Oct 19.

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.

Keywords: Cancer stem-like cell; DNA DSBs; Gold nanoparticle; RBE value.

MeSH terms

  • Cell Cycle
  • Cell Survival
  • Colorectal Neoplasms / pathology*
  • Culture Media, Serum-Free
  • DNA / radiation effects*
  • DNA Breaks, Double-Stranded*
  • Dose-Response Relationship, Radiation
  • Gold / chemistry*
  • HT29 Cells
  • Histones / metabolism
  • Humans
  • Metal Nanoparticles / chemistry*
  • Neoplastic Stem Cells / radiation effects*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • X-Rays

Substances

  • Culture Media, Serum-Free
  • H2AX protein, human
  • Histones
  • Gold
  • DNA