Nanoceria protects from alterations in oxidative metabolism and calcium overloads induced by TNFα and cycloheximide in U937 cells: pharmacological potential of nanoparticles

• Published in: Molecular and cellular biochemistry 2014-12, Vol.397 (1-2), p.245-253
• Main Authors: González-Flores, David, De Nicola, Milena, Bruni, Emanuele, Caputo, Fanny, Rodríguez, Ana B., Pariente, José A., Ghibelli, Lina
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Antifungal Agents - pharmacology; Antioxidants; Apoptosis; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Calcium - metabolism; Cardiology; Cerium - pharmacology; Chromans - pharmacology; Cyclohexane; Cycloheximide - pharmacology; Cysteine; Free Radical Scavengers - pharmacology; Humans; Life Sciences; Medical Biochemistry; Membrane Potential, Mitochondrial - drug effects; Mitochondrial DNA; Nanoparticles; Non-Hodgkin's lymphomas; Oncology; Physiological aspects; Reactive Oxygen Species - metabolism; Tumor necrosis factor; Tumor Necrosis Factor-alpha - pharmacology; U937 Cells
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-014-2192-2

The present study is aimed to determine the protective effect of a novel nanoparticle with antioxidant properties, nanoceria, on reactive oxygen species (ROS) production, and calcium signaling evoked by the tumor necrosis factor-alpha (TNFα) in combination with cycloheximide (CHX) on apoptosis in the human histiocytic lymphoma cell line U937. Our results show that treatment of U937 cells with 10 ng/mL TNFα in combination with 1 μg/mL CHX led to several Ca 2+ alterations. These stimulatory effects on calcium signals were followed by intracellular ROS production and mitochondria membrane depolarization, as well as a time-dependent increase in caspase-8 and -9 activities. Our results show that the pretreatment with well known antioxidants such as trolox and N-acetyl cysteine (NAC) partially reduced the apoptotic effects due to the administration of TNFα plus cycloheximide. Furthermore, nanoceria had a stronger protective effect than trolox or NAC. Our findings also suggest that TNFα plus cycloheximide-induced apoptosis is dependent on alterations in cytosolic concentration of calcium [Ca 2+ ] c and ROS generation in human histiocytic U937 cells.