Cytotoxic Phenanthroline Derivatives Alter Metallostasis and Redox Homeostasis in Neuroblastoma Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Dec 18

PMID 30555630

Citations 6

Authors

Irina Naletova

Cristina Satriano

Alessandra Curci

Nicola Margiotta

Giovanni Natile

Giuseppe Arena

Diego La Mendola

Vincenzo Giuseppe Nicoletti

Enrico Rizzarelli

Affiliations

Soon will be listed here.

Abstract

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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