DNA damage enhancement by radiotherapy-activated hafnium oxide nanoparticles improves cGAS-STING pathway activation in human colorectal cancer cells

Radiother Oncol. 2019 Dec:141:262-266. doi: 10.1016/j.radonc.2019.07.029. Epub 2019 Aug 19.

Abstract

The cGAS-STING pathway can be activated by radiation induced DNA damage and because of its important role in anti-cancer immunity activation, methods to increase its activation in cancer cells could provide significant therapeutic benefits for patients. We explored the impact of hafnium oxide nanoparticles (NBTXR3) activated by radiotherapy on cell death, DNA damage, and activation of the cGAS-STING pathway. We demonstrate that NBTXR3 activated by radiotherapy enhances cell destruction, DNA double strand breaks, micronuclei formation and cGAS-STING pathway activation in a human colorectal cancer model, compared to radiotherapy alone.

Keywords: Colorectal cancer; NBTXR3; Nanoparticle; Radiotherapy; cGAS-STING.

MeSH terms

  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / radiotherapy*
  • DNA Damage*
  • HCT116 Cells
  • Hafnium / pharmacology*
  • Humans
  • Membrane Proteins / physiology*
  • Nanoparticles*
  • Nucleotidyltransferases / physiology*
  • Oxides / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Membrane Proteins
  • Oxides
  • STING1 protein, human
  • hafnium oxide
  • Nucleotidyltransferases
  • cGAS protein, human
  • Hafnium