[The p53 Tumor Suppressor and Copper Metabolism: An Unrevealed but Important Link].

The balance of redox reactions and the fate of the tumor cell are closely related to the regulation of intracellular homeostasis of transition metals, among which copper and its compounds play a key role. Elevated levels of intracellular copper may be a cause and/or consequence of malignancy, since the metabolism of this metal affects the functioning of the electron transport chain, transcription regulation, cell growth, and migration. This wide range of actions is used in antitumor therapy: ROS generation and apoptosis mediated by copper addition, copper deprivation by chelators, and targeted inhibition of specific participants in the copper metabolism chain effectively reduce the survival of tumor cells. However, the exact mechanisms of influence on the cell cycle and cell death behind the activity of copper-associated drugs are still largely unexplored. Numerous attempts to identify them led to the identification of the induction of oxidative stress and the activation of apoptotic cascades via the p53 tumor suppressor, an integral attribute of the action of such compounds. At the same time, the influence of p53, apparently also extends onto the activity of copper metabolism proteins, mediating the processes of antioxidant protection and survival. More and more research data confirm that the interaction of copper and p53 is multifaceted and is not limited solely to ROS. The purpose of this review is to describe how p53 regulation is related to copper metabolic pathways and how this interaction can be used to improve the effectiveness of oncotherapy.

Metal-derived nanoparticles in tumor theranostics: Potential and limitations.

Initially, metal derived nanoparticles have been used exclusively as contrasting agents in magnetic resonance imaging. Today, green routes of chemical synthesis together with numerous modifications of the core and surface gave rise to a plethora of biomedical applications of metal derived nanoparticles including tumor imaging, diagnostics, and therapy. These materials are an emerging class of tools for tumor theranostics. Nevertheless, the spectrum of clinically approved metal nanoparticles remains narrow, as the safety, specificity and efficiency still have to be improved. In this review we summarize the major directions for development and biomedical applications of metal based nanoparticles and analyze their effects on tumor cells and microenvironment. We discuss the advantages and possible limitations of metal nanoparticle-based tumor theranostics, as well as the potential strategies to improve the in vivo performance of these unique materials.