FeSO₄ Induces Apoptosis In Melanoma Cells Via ROS And Mitochondrial Pathway

As an essential element of living organisms,iron participates in many biological processes,such as cell proliferation,growth,metabolism,and death.Importantly,iron is a component of some enzymes in cells,in which iron has a potentially toxic effect in an oxygen-rich environment,through exchange between the reduced state of iron(?)and the oxidation state of iron(?),which finally influences the level of reactive oxygen species(ROS)in cells.In the current study,we demonstrate different roles of iron that was recognized as an initiator and mediator of cell death.Melanoma is recognized as one of the most malignant tumors,associated with the poor prognosis,and resistant to radiochemotherapy and most of antitumor drugs.For these reasons,we hope to find some potential compounds that can be easily absorbed and utilized by human body as an anti-tumor agent or drug sensitizers.In this study,we found that melanoma cells were insensitive to CCCP,a mitochondrial depolarizing drug,because of a lack of Parkin.However,a combination of CCCP and FeSO4 could cause serious death of tumor cells.And this induction of death depended on a sharp increase of cellular ROS,resulting in changes in mitochondrial structure and dysfunction,the release of cytochrome C,then the activation of caspases-9 and the cleavage of caspase-3,which further cleaved intracellular functions and skeleton proteins,ultimately led cells to irreversible death.At the same time,we also found some inhibitors that could block FeSO4 and CCCP induced cell death.In summary,we have showed that FeSO4 can be used to enhance the efficiency of a series of drugs which can depolarized mitochondria to induce malignant melanoma cells' death,which is expected to develop a new potential clinical therapy.