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Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity

Authorized Users Only
2015
Authors
Pesic, Milica
Podolski-Renic, Ana
Stojković, Sonja
Matović, Branko
Zmejkoski, Danica
Kojić, Vesna
Bogdanović, Gordana
Pavicević, Aleksandra
Mojović, Miloš
Savić, Aleksandar G
Milenković, Ivana
Kalauzi, Aleksandar
Radotić, Ksenija
Article (Published version)
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Abstract
Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1... and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine.

Keywords:
Oxygen vacancies / Free radicals / Flow cytometry / Electron spin resonance spectroscopy / Cytotoxicity / Cerium oxide
Source:
Chemico-Biological Interactions, 2015, 232, 85-93
Publisher:
  • Elsevier Ireland Ltd, Clare
Funding / projects:
  • Synthesis, processing and characterization of nanostructured materials for application in the field of energy, mechanical engineering, environmental protection and biomedicine (RS-45012)
  • Identification of predictive molecular markers for cancer progression, response to therapy and disease outcome (RS-41031)
  • Biomarkers in neurodegenerative and malignant processes (RS-41005)
  • Functional, Functionalized and Advanced Nanomaterials (RS-45005)

DOI: 10.1016/j.cbi.2015.03.013

ISSN: 0009-2797

PubMed: 25813935

WoS: 000353741300011

Scopus: 2-s2.0-84925815621
[ Google Scholar ]
117
85
URI
http://rimsi.imsi.bg.ac.rs/handle/123456789/931
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Institut za multidisciplinarna istraživanja
TY  - JOUR
AU  - Pesic, Milica
AU  - Podolski-Renic, Ana
AU  - Stojković, Sonja
AU  - Matović, Branko
AU  - Zmejkoski, Danica
AU  - Kojić, Vesna
AU  - Bogdanović, Gordana
AU  - Pavicević, Aleksandra
AU  - Mojović, Miloš
AU  - Savić, Aleksandar G
AU  - Milenković, Ivana
AU  - Kalauzi, Aleksandar
AU  - Radotić, Ksenija
PY  - 2015
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/931
AB  - Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine.
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-Biological Interactions
T1  - Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity
EP  - 93
SP  - 85
VL  - 232
DO  - 10.1016/j.cbi.2015.03.013
ER  - 
@article{
author = "Pesic, Milica and Podolski-Renic, Ana and Stojković, Sonja and Matović, Branko and Zmejkoski, Danica and Kojić, Vesna and Bogdanović, Gordana and Pavicević, Aleksandra and Mojović, Miloš and Savić, Aleksandar G and Milenković, Ivana and Kalauzi, Aleksandar and Radotić, Ksenija",
year = "2015",
abstract = "Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-Biological Interactions",
title = "Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity",
pages = "93-85",
volume = "232",
doi = "10.1016/j.cbi.2015.03.013"
}
Pesic, M., Podolski-Renic, A., Stojković, S., Matović, B., Zmejkoski, D., Kojić, V., Bogdanović, G., Pavicević, A., Mojović, M., Savić, A. G., Milenković, I., Kalauzi, A.,& Radotić, K.. (2015). Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. in Chemico-Biological Interactions
Elsevier Ireland Ltd, Clare., 232, 85-93.
https://doi.org/10.1016/j.cbi.2015.03.013
Pesic M, Podolski-Renic A, Stojković S, Matović B, Zmejkoski D, Kojić V, Bogdanović G, Pavicević A, Mojović M, Savić AG, Milenković I, Kalauzi A, Radotić K. Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. in Chemico-Biological Interactions. 2015;232:85-93.
doi:10.1016/j.cbi.2015.03.013 .
Pesic, Milica, Podolski-Renic, Ana, Stojković, Sonja, Matović, Branko, Zmejkoski, Danica, Kojić, Vesna, Bogdanović, Gordana, Pavicević, Aleksandra, Mojović, Miloš, Savić, Aleksandar G, Milenković, Ivana, Kalauzi, Aleksandar, Radotić, Ksenija, "Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity" in Chemico-Biological Interactions, 232 (2015):85-93,
https://doi.org/10.1016/j.cbi.2015.03.013 . .

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