Targeting ferroptosis for cancer therapy: exploring novel strategies from its mechanisms and role in cancers

Abstract

Ferroptosis is a novel form of non-apoptotic regulated cell death (RCD), with distinct characteristics and functions in physical conditions and multiple diseases such as cancers. Unlike apoptosis and autophagy, this new RCD is an iron-dependent cell death with features of lethal accumulation of reactive oxygen species (ROS) and over production of lipid peroxidation. Excessive iron from aberrant iron metabolisms or the maladjustment of the two main redox systems thiols and lipid peroxidation role as the major causes of ROS generation, and the redox-acrive ferrous (intracellular labile iron) is a crucial factor for the lipid peroxidation. Regulation of ferrroptosis also involves different pathways such as mevalonate pathway, P53 pathway and p62-Keap1-Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. Ferroptosis roles as a double-edged sword either suppressing or promoting tumor progression with the release of multiple signaling molecules in the tumor microenvironment. Emerging evidence suggests ferroptosis as a potential target for cancer therapy and ferroptosis inducers including small molecules and nanomaterials have been developed. The application of ferroptosis inducers also relates to overcoming drug resistance and preventing tumor metastasis, and may become a promising strategy combined with other anticancer therapies. Here, we summarize the ferroptosis characters from its underlying basis and role in cancer, followed by its possible applications in cancer therapies and challenges maintained.

Artemisinin Derivatives Inhibit Non-small Cell Lung Cancer Cells Through Induction of ROS-dependent Apoptosis/Ferroptosis

“…Reactive oxygen species (ROS) plays an important role in cell signal transduction and tissue homeostasis. Excessive ROS triggers the opening of mitochondrial PTP leading to apoptosis and causes lipid peroxidation leading to ferroptosis [19,20]. To investigate whether ROS is a key molecule that mediates artemisinin derivatives' effect on NSCLC cells, we utilized N-Acetyl-L-cysteine (NAC), a ROS scavenger, to block the production of ROS in NSCLC cells.…”

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

“…Although apoptosis is the most studied type of cell death, other mechanisms have historically been identified, including autophagic cell death and necrosis [ 152 ]. In recent years, there have also been discussions about less-known types of non-apoptotic cell death, such as methuosis, ferroptosis, necroptosis, pyroptosis, and others [ 153 , 154 , 155 , 156 , 157 ]. Next, we deal with the mechanism of demise of the cells caused by chalcones.…”

A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma

“…In the past few years, ferroptosis has been found to be a promising trigger option for cancer cell death, especially for malignant tumors that are resistant to traditional therapies [ 9 , 10 , 11 ]. Ferroptosis is a double-edged sword in tumor development because ferroptotic cancer cells release a variety of signaling molecules, either to inhibit tumor growth or to promote tumor proliferation [ 12 ]. The role of the signals released from ferroptotic cancer cells in tumor microenvironment needs further investigation [ 12 ].…”

“…Ferroptosis is a double-edged sword in tumor development because ferroptotic cancer cells release a variety of signaling molecules, either to inhibit tumor growth or to promote tumor proliferation [ 12 ]. The role of the signals released from ferroptotic cancer cells in tumor microenvironment needs further investigation [ 12 ]. A recent report suggests that ferroptosis suppress metastasis in blood, but ferroptosis is suppressed in the lymph [ 13 ].…”