Role of oxidative and nitro-oxidative damage in silver nanoparticles cytotoxic effect against human pancreatic ductal adenocarcinoma cells

Ewelina Barcińska , Justyna Wierzbicka , Agata Zauszkiewicz-Pawlak , Dagmara Jacewicz , Aleksandra Dąbrowska , Iwona Inkielewicz-Stepniak


Pancreatic ductal adenocarcinoma is one of the most aggressive human malignancies, where the 5-year survival rate is less than 4% worldwide. Successful treatment of pancreatic cancer is a challenge for today’s oncology. Several studies showed that increased levels of oxidative stress may cause cancer cells damage and death. Therefore, we hypothesized that oxidative as well as nitro-oxidative stress is one of the mechanisms inducing pancreatic cancer programmed cell death. We decided to use silver nanoparticles (AgNPs) (2.6 and 18 nm) as a key factor triggering the reactive oxygen species (ROS) and reactive nitrogen species (RNS) in pancreatic ductal adenocarcinoma cells (PANC-1). Previously, we have found that AgNPs induced PANC-1 cells death. Furthermore, it is known that AgNPs may induce an accumulation of ROS and alteration of antioxidant systems in different type of tumors, and they are indicated as promising agents for cancer therapy. Then, the aim of our study was to evaluate the implication of oxidative and nitro-oxidative stress in this cytotoxic effect of AgNPs against PANC-1 cells. We determined AgNP-induced increase of ROS level in PANC-1 cells and pancreatic noncancer cell (hTERT-HPNE) for comparison purposes. We found that the increase was lower in noncancer cells. Reduction of mitochondrial membrane potential and changes in the cell cycle were also observed. Additionally, we determined the increase in RNS level: nitric oxide (NO) and nitric dioxide (NO2) in PANC-1 cells, together with increase in family of nitric oxide synthases (iNOS, eNOS, and nNOS) at protein and mRNA level. Disturbance of antioxidant enzymes: superoxide dismutase (SOD1, SOD2, and SOD3), glutathione peroxidase (GPX-4) and catalase (CAT) were proved at protein and mRNA level. Moreover, we showed cells ultrastructural changes, characteristic for oxidative damage. Summarizing, oxidative and nitro-oxidative stress and mitochondrial disruption are implicated in AgNPs-mediated death in human pancreatic ductal adenocarcinoma cells.
Author Ewelina Barcińska - [Gdanski Uniwersytet Medyczny]
Ewelina Barcińska,,
- Gdanski Uniwersytet Medyczny
, Justyna Wierzbicka - [Gdanski Uniwersytet Medyczny]
Justyna Wierzbicka,,
- Gdanski Uniwersytet Medyczny
, Agata Zauszkiewicz-Pawlak - [Gdanski Uniwersytet Medyczny]
Agata Zauszkiewicz-Pawlak,,
- Gdanski Uniwersytet Medyczny
, Dagmara Jacewicz (FCh / DGICh / LPCC)
Dagmara Jacewicz,,
- Laboratory of Physicochemistry of Coordination Complexes
, Aleksandra Dąbrowska (FCh / KChBionieorg. / LII)
Aleksandra Dąbrowska,,
- Laboratory of Intermolecular Interactions
, Iwona Inkielewicz-Stepniak - [Gdanski Uniwersytet Medyczny]
Iwona Inkielewicz-Stepniak,,
- Gdanski Uniwersytet Medyczny
Journal seriesOxidative Medicine and Cellular Longevity, ISSN 1942-0900, (A 30 pkt)
Issue year2018
Publication size in sheets0.7
Article number8251961
Keywords in Englishoxidative and nitro-oxidative damage, pancreatic ductal adenocarcinoma cells, nitric oxide, nitric dioxide
ASJC Classification2700 General Medicine; 1302 Ageing; 1303 Biochemistry; 1307 Cell Biology
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)30
Score sourcejournalList
ScoreMinisterial score = 30.0, 29-05-2020, ArticleFromJournal
Publication indicators WoS Citations = 4; Scopus Citations = 11; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.315; WoS Impact Factor: 2018 = 4.868 (2) - 2018=5.392 (5)
Citation count*10 (2020-05-20)
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