Research Papers:

Cytotoxic phenanthroline derivatives alter metallostasis and redox homeostasis in neuroblastoma cells

Irina Naletova, Cristina Satriano, Alessandra Curci, Nicola Margiotta, Giovanni Natile, Giuseppe Arena, Diego La Mendola, Vincenzo Giuseppe Nicoletti and Enrico Rizzarelli _

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Oncotarget. 2018; 9:36289-36316. https://doi.org/10.18632/oncotarget.26346

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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

Correspondence to:

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.

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