title: Multiwalled carbon nanotube buckypaper induces cell cycle arrest and apoptosis in human leukemia cell lines through modulation of AKT and MAPK signaling pathways.
abstract: MWCNT buckypaper (BP) shows physico-chemical and mechanical properties that make it potentially useful as a substrate in nano-bio interface research including in tissue engineering. When used as a scaffold material, BP comes into contact with host cells and surrounding tissues; therefore it is critical to determine its biocompatibility and interaction with living systems. The aim of this study was to investigate BP effects on cell growth, apoptosis and reactive oxygen species (ROS) production in three human leukemia cell lines HL-60, U-937 and K-562. BP was able to induce both the reduction of cell proliferation, associated with an arrest in G0/G1 phase of cell cycle and the increase of apoptosis in leukemic cell lines, thus exerting both cytostatic and cytotoxic effects. The growth inhibitory effect was likely mediated by the decrease of cyclins D, E, A, B1 levels and CDK4 expression; meanwhile, the apoptotic effect, not mediated by ROS production, was presumably due to the combined action of the survival and pro-apoptotic AKT and MAPK signal transduction pathways. These results raised the issue of biocompatibility of MWCNT BP for the creation of carbon nanotubes based scaffolds to utilize as prostheses in tissue engineering.
authors.affiliation: Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Dinicola
authors.affiliation: Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Masiello
authors.affiliation: Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Proietti
authors.affiliation: Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy; Azienda Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Coluccia
authors.affiliation: Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy; Department of Experimental Medicine, Sapienza University of Rome, Systems Biology Group Lab, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Gianmarco
authors.initials: G
authors.lastname: Fabrizi
authors.affiliation: Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy; Department of Experimental Medicine, Sapienza University of Rome, Systems Biology Group Lab, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palombo
authors.affiliation: INFN-Laboratori Nazionali di Frascati, Via Enrico Fermi 40, 00044 Frascati, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Micciulla
authors.affiliation: INFN-Laboratori Nazionali di Frascati, Via Enrico Fermi 40, 00044 Frascati, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bistarelli
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ricci
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Catizone
authors.affiliation: Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy; Azienda Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: De Toma
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Systems Biology Group Lab, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Bizzarri
authors.affiliation: INFN-Laboratori Nazionali di Frascati, Via Enrico Fermi 40, 00044 Frascati, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bellucci
authors.affiliation: Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy; Azienda Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy. Electronic address: alessandra.cucina@uniroma1.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cucina
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007938:Leukemia; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D037742:Nanotubes, Carbon / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: AKT; Cell cycle; Cyclins; Leukemia cell lines; MAPKs; MWCNT Buckypaper