title: Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity.
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 Ce(3+) and O(2-) 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 μM. 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.
authors: Institute for Biological Research "Siniša Stanković", University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia. Electronic address: camala@ibiss.bg.ac.rs.
authors: Milica
authors: M
authors: Pešić
authors: Institute for Biological Research "Siniša Stanković", University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia.
authors: Ana
authors: A
authors: Podolski-Renić
authors: Institute for Biological Research "Siniša Stanković", University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia.
authors: Sonja
authors: S
authors: Stojković
authors: Department of Material Science, Vinča Institute of Nuclear Sciences, Vinča, Serbia.
authors: Branko
authors: B
authors: Matović
authors: Department of Material Science, Vinča Institute of Nuclear Sciences, Vinča, Serbia.
authors: Danica
authors: D
authors: Zmejkoski
authors: Institute of Oncology Sremska Kamenica, Sremska Kamenica, Serbia.
authors: Vesna
authors: V
authors: Kojić
authors: Institute of Oncology Sremska Kamenica, Sremska Kamenica, Serbia.
authors: Gordana
authors: G
authors: Bogdanović
authors: Faculty for Physical Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia.
authors: Aleksandra
authors: A
authors: Pavićević
authors: Faculty for Physical Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia.
authors: Miloš
authors: M
authors: Mojović
authors: Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11000 Belgrade, Serbia.
authors: Aleksandar
authors: A
authors: Savić
authors: Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11000 Belgrade, Serbia.
authors: Ivana
authors: I
authors: Milenković
authors: Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11000 Belgrade, Serbia.
authors: Aleksandar
authors: A
authors: Kalauzi
authors: Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11000 Belgrade, Serbia. Electronic address: xenia@imsi.bg.ac.rs.
authors: Ksenija
authors: K
authors: Radotić
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002563:Cerium / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D014216:Triacetoneamine-N-Oxyl / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D014216:Triacetoneamine-N-Oxyl; D002563:Cerium; C030583:ceric oxide
keywords: Cerium oxide; Cytotoxicity; Electron spin resonance spectroscopy; Flow cytometry; Free radicals; Oxygen vacancies