Artykuł w czasopiśmie
Brak miniatury
Licencja
ClosedAccessDostęp zamknięty
 

Analysis of Chromatin Opening in Heterochromatic Non-Small Cell Lung Cancer Tumor-Initiating Cells in Relation to DNA-Damaging Antitumor Treatment

Uproszczony widok
dc.abstract.enPurpose We previously reported that sphere-forming non-small cell lung cancer (NSCLC) tumor-initiating cells (TICs) have an altered activation of DNA damage response- and repair proteins and are refractory to DNA-damaging treatments. We analyzed whether chromatin organization plays a role in the observed refractoriness. Methods and Materials Bulk cells and TICs from the NSCLC H23 and H1299 cell lines were examined using cell viability, clonogenic survival, Western blot, short interfering RNA analysis, and micronucleus assay. Results NSCLC TICs displayed elevated heterochromatin markers trimethylated lysine 9 of histone H3 and heterochromatin protein 1γ relative to bulk cells and reduced cell viability upon histone deacetylase inhibition (HDACi). Vorinostat and trichostatin A increased the euchromatin markers acetylated lysine 9/14 of histone H3 and lysine 8 of histone H4, and HDACi pretreatment increased the phosphorylation of the DNA damage response proteins ataxia telangiectasia mutated and DNA-dependent protein kinase, catalytic subunit, upon irradiation in TICs. HDACi sensitized TICs to cisplatin and to some extent to ionizing irradiation. The protectiveness of a dense chromatin structure was indicated by an enhanced frequency of micronuclei in TICs following irradiation, after knockdown of heterochromatin protein 1γ. Conclusions Although confirmatory studies in additional NSCLC model systems and with respect to analyses of other DNA damage response proteins are needed, our data point toward a heterochromatic structure of NSCLC TICs, such that HDACi can sensitize TICs to DNA damage.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorBrzozowska-Wardecka, Beata
dc.contributor.authorLewensohn, Rolf
dc.contributor.authorViktorsson, Kristina
dc.contributor.authorLundholm, Lovisa
dc.contributor.authorWójcik, Andrzej
dc.contributor.authorEriksson, Mina
dc.contributor.authorHååg, Petra
dc.contributor.authorLipka, Magdalena
dc.contributor.authorLisowska, Halina
dc.date.accessioned2024-01-24T16:29:19Z
dc.date.available2024-01-24T16:29:19Z
dc.date.issued2018
dc.description.financeNie dotyczy
dc.description.number1
dc.description.volume100
dc.identifier.doi10.1016/J.IJROBP.2017.09.033
dc.identifier.issn0360-3016
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/100610
dc.identifier.weblinkhttps://www.sciencedirect.com/science/article/pii/S0360301617339330
dc.languageeng
dc.pbn.affiliationphysical sciences
dc.relation.ispartofInternational Journal of Radiation Oncology Biology Physics
dc.relation.pages174-187
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleAnalysis of Chromatin Opening in Heterochromatic Non-Small Cell Lung Cancer Tumor-Initiating Cells in Relation to DNA-Damaging Antitumor Treatment
dc.typeJournalArticle
dspace.entity.typePublication