Multiwalled carbon nanotube buckypaper induces cell cycle arrest and apoptosis in human leukemia cell lines through modulation of AKT and MAPK signaling pathways

Simona Dinicola; Maria Grazia Masiello; Sara Proietti; Pierpaolo Coluccia; Gianmarco Fabrizi; Alessandro Palombo; Federico Micciulla; Silvia Bistarelli; Giulia Ricci; Angela Catizone; Giorgio De Toma; Mariano Bizzarri; Stefano Bellucci; Alessandra Cucina

doi:10.1016/j.tiv.2015.05.006

Multiwalled carbon nanotube buckypaper induces cell cycle arrest and apoptosis in human leukemia cell lines through modulation of AKT and MAPK signaling pathways

Toxicol In Vitro. 2015 Oct;29(7):1298-308. doi: 10.1016/j.tiv.2015.05.006. Epub 2015 May 18.

Affiliations

¹ 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.
² 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.
³ 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.
⁴ INFN-Laboratori Nazionali di Frascati, Via Enrico Fermi 40, 00044 Frascati, Rome, Italy.
⁵ Department of Experimental Medicine, Second University of Naples, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy.
⁶ Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.
⁷ Department of Experimental Medicine, Sapienza University of Rome, Systems Biology Group Lab, Viale Regina Elena 324, 00161 Rome, Italy.
⁸ 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.

PMID: 25998161
DOI: 10.1016/j.tiv.2015.05.006

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.

Keywords: AKT; Cell cycle; Cyclins; Leukemia cell lines; MAPKs; MWCNT Buckypaper.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Cell Cycle Checkpoints / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Humans
Leukemia
Mitogen-Activated Protein Kinases / metabolism*
Nanotubes, Carbon / toxicity*
Proto-Oncogene Proteins c-akt / metabolism*
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects

Substances

Nanotubes, Carbon
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinases