Copper as a Target for Treatment of Neuroblastoma: Molecular and Cellular Mechanisms

Copper is a trace metal essential to the catalysis of a wide range of enzymatic activities, including those involved in the process of energy production (cytochrome c oxidase), the cell response to oxidant injuries (Cu,Zn-superoxide dismutase), the catecholamine (dopamine βmonooxygenase) and melanin (tyrosinase) production, the remodelling of extracellular matrix (lysyl oxidase), blood clotting processes (Factors V and VIII) and iron metabolism (ceruloplas‐ min and hephaestin) [1]. The catalytic properties of copper are linked to its ability to easily assume the oxidized (Cu2+) and reduced (Cu+) states, but just the metal reactive behaviour can trigger severe cell alterations through the generation of hydroxyl radicals in Fenton-like reactions [2,3]. When the cytosolic copper concentration is above the optimal level, the newly formed reactive oxygen species (ROS) rapidly bind to DNA, thus inducing the breaking of the nucleic acid strands and initiating a series of cascade events that can lead to significant damage to cell structures and function [4].