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Cerium oxide nanoparticles reestablish cell integrity checkpoints and apoptosis competence in irradiated HaCaT cells via novel redox-independent activity

TitleCerium oxide nanoparticles reestablish cell integrity checkpoints and apoptosis competence in irradiated HaCaT cells via novel redox-independent activity
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2018
AuthorsCaputo, F., Giovanetti Anna, Corsi F., Maresca V., Briganti S., Licoccia S., Traversa E., and Ghibelli L.
JournalFrontiers in Pharmacology
Volume9
ISSN16639812
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.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85055197634&doi=10.3389%2ffphar.2018.01183&partnerID=40&md5=1c6ade2089f64a2e596fe6f2694d800f
DOI10.3389/fphar.2018.01183
Citation KeyCaputo2018