Cytotoxicity and mechanism of action of metal complexes: An overview

After the discovery of cisplatin, many metal compounds were investigated for the therapy of diseases, especially cancer. The high therapeutic potential of metal-based compounds is related to the special properties of these compounds, such as their redox activity and ability to target vital biological sites. The overproduction of ROS and the consequent destruction of the membrane potential of mitochondria and/or the DNA helix is one of the known pathways leading to the induction of apoptosis by metal complexes. The apoptosis process can occur via the death receptor pathway and/or the mitochondrial pathway. The expression of Bcl2 proteins and the caspase family play critical roles in these pathways. In addition to apoptosis, autophagy is another process that regulates the suppression or promotion of various cancers through a dual action. On the other hand, the ability to interact with DNA is an important property found in several metal complexes with potent antiproliferative effects against cancer cells. These interactions were classified into two important categories: covalent/coordinated or subtle, and non-coordinated interactions. The anticancer activity of metal complexes is sometimes achieved by the simultaneous combination of several mechanisms. In this review, the anticancer effect of metal complexes is mechanistically discussed by different pathways, and some effective agents on their antiproliferative properties are explained.

Automated summary

After the discovery of cisplatin, many metal compounds have been explored for cancer therapy due to their special properties, such as redox activity and targeting ability. Metal complexes induce apoptosis through the overproduction of ROS, leading to the disruption of mitochondrial membrane potential or DNA helix. Apoptosis can occur via death receptor pathway or mitochondrial pathway, regulated by Bcl2 proteins and the caspase family. Metal complexes also interact with DNA through covalent/coordinated or subtle, and non-coordinated interactions, contributing to their potent antiproliferative effects against cancer cells. The review discusses the mechanistic anticancer effects of metal complexes through different pathways and highlights effective agents with antiproliferative properties.