Ferroptosis: A Mechanism of Cell Death With Potential Scope in Cancer Therapy

Abstract

Ferroptosis is a type of regulated cell death caused by oxidative imbalance of the intracellular microenvironment. This causes the accumulation of toxic lipid peroxides, depicted by iron overload and lipid peroxidation, which results in disease development. The affected cell population displays unique morphological and biochemical features, which are distinct from other modes of cell death, like apoptosis, pyroptosis, and necroptosis. The individual pathways of each of these modes are interrelated and tend to counterbalance each other in the mechanism of cell death. The process of ferroptosis is associated with disturbances in iron metabolism, in conjunction with glutathione peroxidase and lipid peroxidation, culminating in a reduction of antioxidant capacity and accumulation of lipid peroxides in the dying cell. It has been observed that even excess cellular levels of iron can cause cell death, where ferroptosis is initiated by diminishing the levels of glutathione and glutathione peroxidase 4, and thus leading to excess build-up of lipid reactive oxygen species (ROS). In the case of a neoplastic cell, ferroptosis along with its regulators tends to orchestrate cell death and also affects cancer progression by modulation of proliferation activity, apoptosis suppression, metastasis, and drug resistance. Comprehending the complex network of molecular processes implicated in ferroptosis regulation is vital for developing targeted therapies for diseases where ferroptosis plays a significant role.

Keywords: cancer; ferroptosis; iron metabolism; mitochondria.