Mitochondrial fusion: A mechanism of cisplatin-induced resistance in neuroblastoma cells?

• Published in: Neurotoxicology (Park Forest South) Vol. 34; pp. 51 - 60
• Main Authors: Santin, Giada, Piccolini, Valeria M., Barni, Sergio, Veneroni, Paola, Giansanti, Vincenzo, Dal Bo, Veronica, Bernocchi, Graziella, Bottone, Maria Grazia
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.01.2013; Elsevier
• Subjects: Actins - metabolism; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis Inducing Factor - metabolism; B50 neuroblastoma rat cells; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Cisplatin; Cisplatin - pharmacology; Cytochromes c - metabolism; DNA, Mitochondrial - metabolism; Drug resistance; Drug Resistance, Neoplasm; Flow Cytometry; GTP Phosphohydrolases - metabolism; Medical sciences; Membrane Potential, Mitochondrial - drug effects; Microscopy, Confocal; Microscopy, Electron, Transmission; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial Dynamics - drug effects; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neurology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Sirtuin 1 - metabolism; Time Factors; Toxicology; Tumors of the nervous system. Phacomatoses; Mitochondria; B50 neuroblastoma rat cells; Drug resistance; cisPt; Cisplatin; Apoptosis; Antineoplastic agent; Nervous system diseases; Treatment resistance; Rat; Rodentia; Malignant tumor; Neuroblastoma; In vitro; Alkylating agent; Vertebrata; Mammalia; Cell death; Animal; Autonomic neuropathy; Mechanism of action; Cancer; Platinum II Complexes
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2012.10.011

► Cisplatin induces neurotoxicity in neuroblastoma rat cells through apoptotic pathways. ► Cisplatin activates morphological alterations in mitochondria. ► Mitochondrial elongation could be a mechanism of drug resistance. Cisplatin induces apoptosis through different pathways. The intrinsic apoptotic pathway is mediated by mitochondria, which, as a result of cisplatin treatment, undergo morphological alterations. The aim of this study was to investigate cisplatin-induced mitochondrial functional and morphological long-term effects in neuroblastoma B50 rat cells. To this purpose, we followed evaluated different several apoptotic markers by means of flow cytometry, confocal and electron microscopy and western blotting techniques. We applied different treatment protocols based on the incubation of the neuroblastoma B50 rat cells with 40μM cisplatin: (i) for 48h and harvesting of the cells at the end of the treatment; (ii) further recovery in drug-free medium for 7 days post-treatment; (iii) conditions as in (ii) followed by re-seeding in normal medium and growth for a further 4 days. We observed apoptosis induction after the first treatment and after the recovery from cell death after long-term culture in drug-free medium. Interestingly, the latter phenomenon was characterized by mitochondrial elongation and mitochondrial protein rearrangement. In recovered and re-seeded cells, mitochondrial equilibrium moved toward fusion, possibly protecting cells from apoptosis.