What is ferroptosis?4 answersFerroptosis is a form of regulated cell death characterized by the accumulation of toxic lipid peroxides, particularly in the plasma membrane, leading to lytic cell death. It is triggered by iron-dependent lipid peroxidation and is distinct from other types of cell death by function and morphology. Ferroptosis has been associated with various pathological conditions, including infection, sterile inflammation, tumor immunity, cellular metabolism, neurodegenerative diseases, cardiovascular diseases, and ischemia-reperfusion injuries. It has also been linked to cardiac diseases, with mitochondria playing a crucial role in regulating ferroptosis and protecting against mitochondrial cardiomyopathy. Additionally, ferroptosis has been implicated in autoimmune disorders, such as autoimmune hepatitis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Parkinson's Disease, psoriasis, and insulin-dependent diabetes mellitus. Targeting ferroptosis may have therapeutic potential for treating these diseases.
What cell types are susceptible to ferroptosis?5 answersFerroptosis is a form of cell death that can affect various cell types. Immune cell-secreted cytokines can either increase or suppress ferroptosis sensitivities of other cell types, such as tumor cells and fibroblasts. Ferroptotic cell-released factors can also modulate the functions of neighboring immune cells, including dendritic cells, macrophages, and T cells. Ferroptosis has been associated with neurodegenerative diseases, carcinogenesis, stroke, intracerebral haemorrhage, traumatic brain injury, and ischemia-reperfusion injury. It has also shown therapeutic potential in the treatment of cancer and other diseases. Ferroptosis is a type of regulated cell death that occurs through Fe(II)-dependent lipid peroxidation when the reduction capacity of a cell is insufficient. Therefore, various cell types, including immune cells, tumor cells, fibroblasts, and neurons, are susceptible to ferroptosis.
How does ferroptosis support tumor growth in breast cancer?5 answersFerroptosis, a mode of cell death characterized by excess reactive oxygen species-induced lipid peroxidation, has been implicated in breast cancer progression and therapy. It has been observed that ferroptosis induction successfully eliminates cancer cells that are resistant to other modes of cell death, such as apoptosis. This suggests that ferroptosis may become a new direction for designing breast cancer treatment. Several key regulators of ferroptosis, including glutathione, glutathione peroxidase 4, iron, nuclear factor erythroid-2 related factor-2, superoxide dismutases, lipoxygenase, and coenzyme Q, have been identified in breast cancer. Additionally, traditional drugs against breast cancer have been found to induce ferroptosis, and ferroptosis inducers have been shown to eliminate breast cancer cells. These findings suggest that ferroptosis supports tumor growth in breast cancer by overcoming apoptosis resistance and eliminating therapy-resistant cells.
How does ferroptosis support tumor growth?5 answersFerroptosis supports tumor growth by blocking antitumor immunity and promoting an immunosuppressive microenvironment that promotes tumor growth and progression. It has been found that immunosuppressive neutrophils in the tumor microenvironment undergo ferroptosis, which inhibits the immune response against the tumor. Additionally, the metabolic rewiring of cancer cells, which is critical for their persistence and expansion, can lead to an acquired sensitivity to ferroptosis. This sensitivity to ferroptosis can be exploited as a therapeutic strategy to target therapy-insensitive tumors. Furthermore, the regulation of ferroptosis sensitivity and the modulation of metabolic pathways controlling ferroptosis can reshape the tumor niche, creating an immunosuppressive microenvironment that supports tumor growth. Overall, understanding the mechanisms of ferroptosis and its role in tumor growth can provide insights for developing novel therapeutic strategies to improve cancer treatment.
Is ferroptosis beneficial for metabolic diseases?5 answersFerroptosis has been shown to contribute to the development and progression of metabolic diseases such as diabetes, non-alcoholic fatty liver disease (NAFLD), osteoporosis, and atherosclerosis (AS). It is characterized by iron-dependent lipid peroxidation and is considered a form of programmed cell death. The main molecular mechanisms of ferroptosis involve dysregulation of iron metabolism, mitochondrial dysfunction, impaired antioxidant capacity, and accumulation of lipid-related peroxides. While the exact roles and underlying mechanisms of ferroptosis in metabolic diseases are not fully understood, there is evidence suggesting its involvement in the pathophysiological processes. Targeting ferroptosis has been proposed as a potential therapeutic approach for metabolic diseases. However, further research is needed to fully elucidate the specific physiopathological mechanisms and therapeutic effects of ferroptosis in metabolic diseases.
What promote ferroptosis in cancer?5 answersFerroptosis in cancer is promoted by various factors. Cytochrome P450 2E1 (CYP2E1) induction, which can be caused by genetic polymorphisms or exposure to xenobiotics, contributes to the cellular pool of lipid hydroperoxides (LOOH) and promotes ferroptosis. Autophagy-dependent degradation of proteins and organelles, such as ferritin, SLC40A1, ARNTL, GPX4, and CDH2, induces iron overload and lipid peroxidation, leading to ferroptosis. The upregulation of PTBP1 in liver cancer cells regulates ferroptosis by mediating NCOA4 translation. Additionally, the metal-free polymer photosensitizer BDPB triggers glutathione peroxidase 4 downregulation, lipid peroxide accumulation, and ferroptotic cell death in starved cancer cells. These findings highlight the importance of CYP2E1 induction, autophagy-dependent degradation, PTBP1-NCOA4 axis, and BDPB-induced mechanisms in promoting ferroptosis in cancer.