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Cerium oxide nanoparticles reestablish cell integrity checkpoints and apoptosis competence in irradiated HaCaT cells via novel redox-independent activity
- Source :
- Frontiers in Pharmacology, Frontiers in Pharmacology, Vol 9 (2018)
- Publication Year :
- 2018
- Publisher :
- Frontiers Media S.A., 2018.
-
Abstract
- Cerium oxide nanoparticles (CNPs) are potent radical scavengers protecting cells from oxidative insults, including ionizing radiation. Here we show that CNPs prevent X-ray-induced oxidative imbalance reducing DNA breaks on HaCat keratinocytes, nearly abating mutagenesis. At the same time, and in spite of the reduced damage, CNPs strengthen radiation-induced cell cycle arrest and apoptosis outcome, dropping colony formation; notably, CNPs do not possess any intrinsic toxicity toward non-irradiated HaCat, indicating that they act on damaged cells. Thus CNPs, while exerting their antioxidant action, also reinforce the stringency of damage-induced cell integrity checkpoints, promoting elimination of the “tolerant” cells, being in fact radio-sensitizers. These two contrasting pathways are mediated by different activities of CNPs: indeed Sm-doped CNPs, which lack the Ce3+/Ce4+ redox switch and the correlated antioxidant action, fail to decrease radiation-induced superoxide formation, as expected, but surprisingly maintain the radio-sensitizing ability and the dramatic decrease of mutagenesis. The latter is thus attributable to elimination of damaged cells rather than decreased oxidative damage. This highlights a novel redox-independent activity of CNPs, allowing selectively eliminating heavily damaged cells through non-toxic mechanisms, rather reactivating endogenous anticancer pathways in transformed cells. Copyright © 2018 Caputo, Giovanetti, Corsi, Maresca, Briganti, Licoccia, Traversa and Ghibelli.
- Subjects :
- 0301 basic medicine
Cell cycle checkpoint
Antioxidant
Settore ING-IND/22 - Scienza e Tecnologia dei Materiali
medicine.medical_treatment
Radio-sensitization
Endogeny
Apoptosis
02 engineering and technology
Oxidative phosphorylation
DNA damage response
03 medical and health sciences
chemistry.chemical_compound
medicine
Pharmacology (medical)
DNA integrity checkpoints
Original Research
Pharmacology
Chemistry
Superoxide
Settore CHIM/07 - Fondamenti Chimici delle Tecnologie
Settore BIO/13
lcsh:RM1-950
Mutagenesis
Anticancer therapy
Cerium oxide nanoparticles
Apoptosi
DNA integrity checkpoint
021001 nanoscience & nanotechnology
Cell biology
Cerium oxide nanoparticle
HaCaT
lcsh:Therapeutics. Pharmacology
030104 developmental biology
0210 nano-technology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pharmacology, Frontiers in Pharmacology, Vol 9 (2018)
- Accession number :
- edsair.doi.dedup.....35f219104725050f5fcb321bbd1dcb1a