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Protein disulphide isomerase as a target for nanoparticle-mediated sensitisation of cancer cells to radiation.
- Source :
-
Nanotechnology [Nanotechnology] 2016 May 27; Vol. 27 (21), pp. 215101. Date of Electronic Publication: 2016 Apr 15. - Publication Year :
- 2016
-
Abstract
- Radiation resistance and toxicity in normal tissues are limiting factors in the efficacy of radiotherapy. Gold nanoparticles (GNPs) have been shown to be effective at enhancing radiation-induced cell death, and were initially proposed to physically enhance the radiation dose deposited. However, biological responses of GNP radiosensitization based on physical assumptions alone are not predictive of radiosensitisation and therefore there is a fundamental research need to determine biological mechanisms of response to GNPs alone and in combination with ionising radiation. This study aimed to identify novel mechanisms of cancer cell radiosensitisation through the use of GNPs, focusing on their ability to induce cellular oxidative stress and disrupt mitochondrial function. Using N-acetyl-cysteine, we found mitochondrial oxidation to be a key event prior to radiation for the radiosensitisation of cancer cells and suggests the overall cellular effects of GNP radiosensitisation are a result of their interaction with protein disulphide isomerase (PDI). This investigation identifies PDI and mitochondrial oxidation as novel targets for radiosensitisation.
- Subjects :
- Cell Line, Tumor
Cell Survival drug effects
Cell Survival radiation effects
Gene Expression Regulation, Neoplastic drug effects
Gene Expression Regulation, Neoplastic radiation effects
Gold chemistry
Humans
Membrane Potential, Mitochondrial drug effects
Membrane Potential, Mitochondrial radiation effects
Mitochondria drug effects
Mitochondria radiation effects
Neoplasms drug therapy
Neoplasms radiotherapy
Oxidative Stress radiation effects
Acetylcysteine pharmacology
Gold pharmacology
Metal Nanoparticles chemistry
Neoplasms enzymology
Protein Disulfide-Isomerases metabolism
Radiation-Sensitizing Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1361-6528
- Volume :
- 27
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Nanotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 27080849
- Full Text :
- https://doi.org/10.1088/0957-4484/27/21/215101