Targeting ferroptosis, a novel programmed cell death, for the potential of alcohol-related liver disease therapy

Shi, Jingfen; Liu, Yu’e; Wang, Yan; Gao, Ru; Wang, Yi; Li, Jun

doi:10.3389/fphar.2023.1194343

Cited by 7 publications

(10 citation statements)

References 132 publications

(147 reference statements)

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“…GPX4 is the only enzyme that reduces cholesterol, hydrogen peroxide and oxidized fatty acids. GPX4 can convert reduced GSH to oxidized glutathione and lipid hydrogen peroxide (L-H 2 O 2 , toxic) to lipid alcohols (L-OH, non-toxic), thereby promoting the decomposition of hydrogen peroxide and inhibiting ferroptosis ( 63 , 64 ). This indicated that reduced GPX4 activity favors ferroptosis ( 65 , 66 ).…”

Section: Ferroptosismentioning

confidence: 99%

The role of ferroptosis in radiotherapy and combination therapy for head and neck squamous cell carcinoma (Review)

Feng,

Li,

Yang

et al. 2024

Oncol Rep

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Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive, heterogeneous tumour usually caused by alcohol and tobacco consumption, making it one of the most common malignancies worldwide. Despite the fact that various therapeutic approaches such as surgery, radiation therapy (RT), chemotherapy (CT) and targeted therapy have been widely used for HNSCC in recent years, its recurrence rate and mortality rate remain high. RT is the standard treatment choice for HNSCC, which induces reactive oxygen species production and causes oxidative stress, ultimately leading to tumour cell death. CT is a widely recognized form of cancer treatment that treats a variety of cancers by eliminating cancer cells and preventing them from reproducing. Immune checkpoint inhibitor and epidermal growth factor receptor are important in the treatment of recurrent or metastatic HNSCC. Iron death, a type of cell death regulated by peroxidative damage to phospholipids containing polyunsaturated fatty acids in cell membranes, has been found to be a relevant death response triggered by tumour RT in recent years. In the present review, an overview of the current knowledge on RT and combination therapy and iron death in HNSCC was provided, the mechanisms by which RT induces iron death in tumour cells were summarized, and therapeutic strategies to target iron death in HNSCC were explored. The current review provided important information for future studies of iron death in the treatment of HNSCC.

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Section: Ferroptosismentioning

confidence: 99%

The role of ferroptosis in radiotherapy and combination therapy for head and neck squamous cell carcinoma (Review)

Feng,

Li,

Yang

et al. 2024

Oncol Rep

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“…Alcohol-related liver disease (ALD), the leading global cause of chronic liver disease, involves pathological processes ranging from hepatic steatosis to inflammation, fibrosis, cirrhosis, and HCC [ 112 ]. Increasing evidence suggests that ferroptosis plays an important role in ALD and holds promise as an ideal target [ 113 ]. Alcohol promotes intestinal iron absorption and increases the risk of hepatic iron overload through a synergistic effect with free iron [ 113 ].…”

Section: Nac Treat Liver Disease By Targeting Ferroptosismentioning

confidence: 99%

“…Increasing evidence suggests that ferroptosis plays an important role in ALD and holds promise as an ideal target [ 113 ]. Alcohol promotes intestinal iron absorption and increases the risk of hepatic iron overload through a synergistic effect with free iron [ 113 ]. In addition, acetaldehyde, the major intermediate metabolite of ethanol, is responsible for the generation of ROS and down-regulating the expression of key antioxidant genes such as Nrf2 , thereby impairing the antioxidant system [ 114 ].…”

Section: Nac Treat Liver Disease By Targeting Ferroptosismentioning

confidence: 99%

Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

Wu,

Zhu,

Liu

et al. 2024

Antioxidants

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Ferroptosis is an emerging type of regulated cell death usually accompanied by the accumulation of ferrous ions (Fe2+) and lipid peroxides. As the metabolic hub of the body, the liver is crucial for iron storage and lipid metabolism. The liver seems to be closely related to ferroptosis through iron and lipid metabolism. Liver disease greatly threatens host health, and exploring effective interventions is essential. Mounting studies have demonstrated that ferroptosis is one of the possible pathogenic mechanisms involved in liver disease. Targeting ferroptosis may provide a promising opportunity for treating liver disease. However, drugs targeting ferroptosis are extremely limited. Therefore, it is an urgent need to develop new and safe ferroptosis regulators. Natural active compounds (NAC), especially those derived from traditional Chinese medicine, have recently shown great therapeutic potential in liver disease via modulating ferroptosis-related genes or pathways. Here, we outline the molecular mechanism of ferroptosis and systematically summarize the regulatory function of NAC on ferroptosis in liver disease. Finally, we discuss the application prospects and potential problems concerning NAC as ferroptosis regulators for managing liver disease.

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“…GPX4 leverages the activity of a wide range of reductants to detoxify the oxidative radicals and is thus the main inhibitor of ferroptosis [ 3 , 33 , 34 ]. GSH is the major reducing substrate for GPX4.…”

Section: Regulation Of Ferroptosismentioning

confidence: 99%

The diversified role of mitochondria in ferroptosis in cancer

Liu,

Lu,

et al. 2023

Cell Death Dis

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Ferroptosis is a form of regulated cell death induced by iron-dependent lipid peroxidation, and it has been studied extensively since its discovery in 2012. Induced by iron overload and ROS accumulation, ferroptosis is modulated by various cellular metabolic and signaling pathways. The GSH-GPX4 pathway, the FSP1-CoQ10 pathway, the GCH1-BH4 pathway, the DHODH-CoQH2 system and the sex hormones suppress ferroptosis. Mitochondrial iron metabolism regulates ferroptosis and mitochondria also undergo a morphological change during ferroptosis, these changes include increased membrane density and reduced mitochondrial cristae. Moreover, mitochondrial energy metabolism changes during ferroptosis, the increased oxidative phosphorylation and ATP production rates lead to a decrease in the glycolysis rate. In addition, excessive oxidative stress induces irreversible damage to mitochondria, diminishing organelle integrity. ROS production, mitochondrial membrane potential, mitochondrial fusion and fission, and mitophagy also function in ferroptosis. Notably, some ferroptosis inhibitors target mitochondria. Ferroptosis is a major mechanism for cell death associated with the progression of cancer. Metastasis-prone or metastatic cancer cells are more susceptible to ferroptosis. Inducing ferroptosis in tumor cells shows very promising potential for treating drug-resistant cancers. In this review, we present a brief retrospect of the discovery and the characteristics of ferroptosis, then we discuss the regulation of ferroptosis and highlight the unique role played by mitochondria in the ferroptosis of cancer cells. Furthermore, we explain how ferroptosis functions as a double-edged sword as well as novel therapies aimed at selectively manipulating cell death for cancer eradication.

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Targeting ferroptosis, a novel programmed cell death, for the potential of alcohol-related liver disease therapy

Cited by 7 publications

References 132 publications

The role of ferroptosis in radiotherapy and combination therapy for head and neck squamous cell carcinoma (Review)

The role of ferroptosis in radiotherapy and combination therapy for head and neck squamous cell carcinoma (Review)

Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

The diversified role of mitochondria in ferroptosis in cancer

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