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Silver nanoparticles of different sizes induce a mixed type of programmed cell death in human pancreatic ductal adenocarcinoma

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dc.abstract.enPancreatic ductal adenocarcinoma, with the high resistance to chemotherapeutic agents, remains the fourth leading cause of cancer-death in the world. Due to the wide range of biological activity and unique properties, silver nanoparticles (AgNPs) are indicated as agents with potential to overcome barriers involved in chemotherapy failure. Therefore, in our study we decided to assess the ability of AgNPs to kill pancreatic cancer cells, and then to identify the molecular mechanism underlying this effect. Moreover, we evaluated the cytotoxicity of AgNPs against non-tumor cell of the same tissue (hTERT-HPNE cells) for comparison. Our results indicated that AgNPs with size of 2.6 and 18 nm decreased viability, proliferation and caused death of pancreatic cancer cells in a size- and concentration-dependent manner. Ultrastructural analysis identified that cellular uptake of AgNPs resulted in apoptosis, autophagy, necroptosis and mitotic catastrophe. These alterations were associated with increased pro-apoptotic protein Bax and decreased level of anti-apoptotic protein Bcl-2. Moreover, AgNPs significantly elevated the level of tumor suppressor p53 protein as well as necroptosis- and autophagy-related proteins: RIP-1, RIP-3, MLKL and LC3-II, respectively. In addition, we found that PANC-1 cells were more vulnerable to AgNPs-induced cytotoxicity compared to pancreatic non-tumor cells. In conclusion, AgNPs by inducing mixed type of programmed cell death in PANC-1 cells, could provide a new therapeutic strategy to overcome chemoresistance in one of the deadliest human cancer.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorBARCIŃSKA, EWELINA
dc.contributor.authorInkielewicz-Stępniak, Iwona
dc.contributor.authorZAUSZKIEWICZ-PAWLAK, AGATA
dc.contributor.authorWójcik, Michał
dc.date.accessioned2024-01-26T07:36:57Z
dc.date.available2024-01-26T07:36:57Z
dc.date.copyright2017-11-20
dc.date.issued2018
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number4
dc.description.versionFINAL_PUBLISHED
dc.description.volume9
dc.identifier.doi10.18632/ONCOTARGET.22563
dc.identifier.issn1949-2553
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/119820
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofOncotarget
dc.relation.pages4675-4697
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enpancreas ductal adenocarcinoma cells
dc.subject.ensilver nanoparticles
dc.subject.enautophagy
dc.subject.ennecroptosis
dc.subject.enmitotic catastrophe
dc.titleSilver nanoparticles of different sizes induce a mixed type of programmed cell death in human pancreatic ductal adenocarcinoma
dc.typeJournalArticle
dspace.entity.typePublication