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Cytotoxic phenanthroline derivatives alter metallostasis and redox homeostasis in neuroblastoma cells.

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.

SUBMITTER: Naletova I

PROVIDER: S-EPMC6284747 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Cytotoxic phenanthroline derivatives alter metallostasis and redox homeostasis in neuroblastoma cells.

Naletova Irina I Satriano Cristina C Curci Alessandra A Margiotta Nicola N Natile Giovanni G Arena Giuseppe G La Mendola Diego D Nicoletti Vincenzo Giuseppe VG Rizzarelli Enrico E

Oncotarget 20181120 91

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 ...[more]

PMID: 30555630

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