Cytotoxic phenanthroline derivatives alter metallostasis and redox homeostasis in neuroblastoma cells
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 1244 views | HTML 2819 views | ?
Irina Naletova1,2,*, Cristina Satriano1,2,*, Alessandra Curci2,3, Nicola Margiotta2,3, Giovanni Natile2,3, Giuseppe Arena1,2, Diego La Mendola2,4, Vincenzo Giuseppe Nicoletti2,5 and Enrico Rizzarelli1,2
1Department of Chemical Sciences, University of Catania, Catania, Italy
2Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (CIRCMSB), Bari, Italy
3Department of Chemistry, University of Bari ‘Aldo Moro’, Bari, Italy
4Department of Pharmacy, University of Pisa, Pisa, Italy
5Section of Medical Biochemistry, Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Catania, Italy
*These authors contributed equally to this work
Enrico Rizzarelli, email: [email protected]
Vincenzo Giuseppe Nicoletti, email: [email protected]
Keywords: metal homeostasis; anticancer drug; ionophores; SH-SY5Y cell line; oxidative stress
Received: September 17, 2018 Accepted: November 01, 2018 Published: November 20, 2018
Copper homeostasis is generally investigated focusing on a single component of the metallostasis network. Here we address several of the factors controlling the metallostasis for neuroblastoma cells (SH-SY5Y) upon treatment with 2,9-dimethyl-1,10-phenanthroline-5,6-dione (phendione) and 2,9-dimethyl-1,10-phenanthroline (cuproindione). These compounds bind and transport copper inside cells, exert their cytotoxic activity through the induction of oxidative stress, causing apoptosis and alteration of the cellular redox and copper homeostasis network. The intracellular pathway ensured by copper transporters (Ctr1, ATP7A), chaperones (CCS, ATOX, COX 17, Sco1, Sco2), small molecules (GSH) and transcription factors (p53) is scrutinised.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.