Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(9)
Published: Sept. 23, 2024
Language: Английский
Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)
Published: Oct. 8, 2022
In ferroptosis, the roles of mitochondria have been controversial. To explore role mitochondrial events in we employed DNA-depleted ρ0 cells that are resistant to cell death due enhanced expression antioxidant enzymes. Expression mitochondrial-type GPx4 (mGPx4) but no other forms was increased SK-Hep1 cells. Likely high mGPx4 expression, were ferroptosis by erastin inhibiting xCT channel. contrast, susceptible a concentration RSL3 imposing inhibition. Accumulation cellular ROS and oxidized lipids observed erastin- or RSL3-treated ρ+ not erastin-treated Mitochondrial peroxidized accumulated only also acting on plasma membrane. quenching inhibited dose RSL3, suggesting critical ferroptosis. Ferroptosis more than 20-fold lower MitoQ, quencher, compared DecylQ, non-targeting counterpart. markedly VDAC inhibitor, accompanied significantly reduced accumulation ROS, total lipids, strongly supporting ferroptotic steps induced RSL3. sorafenib suppressed quenchers, abrogation sorafenib-induced lipid accumulation. These results suggest upregulation could be ultimate step determining final fate.
Language: Английский
Citations
100
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: March 12, 2024
Abstract Recent evidence indicates ferroptosis is implicated in the pathophysiology of various liver diseases; however, organ-specific regulation mechanism poorly understood. Here, we demonstrate 7-dehydrocholesterol reductase (DHCR7), terminal enzyme cholesterol biosynthesis, as a regulator hepatocytes. Genetic and pharmacological inhibition (with AY9944) DHCR7 suppress human hepatocellular carcinoma Huh-7 cells. increases its substrate, (7-DHC). Furthermore, exogenous 7-DHC supplementation using hydroxypropyl β-cyclodextrin suppresses ferroptosis. A 7-DHC-derived oxysterol metabolite, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), increased by ferroptosis-inducer RSL-3 -deficient cells, suggesting that ferroptosis-suppressive effect associated with oxidation 7-DHC. Electron spin resonance analysis reveals functions radical trapping agent, thus protecting cells from We further show AY9944 inhibits hepatic ischemia-reperfusion injury, genetic ablation Dhcr7 prevents acetaminophen-induced acute failure mice. These findings provide new insights into regulatory suggest potential therapeutic option for ferroptosis-related diseases.
Language: Английский
Citations
31
Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)
Published: March 13, 2024
Abstract Ferroptosis is an iron ion-dependent, regulatory cell death modality driven by intracellular lipid peroxidation that plays a key role in the development of HCC. Studies have shown various clinical agents (e.g., sorafenib) ferroptosis inducer-like effects and can exert therapeutic modulating different factors pathway. This implies targeting tumor may be very promising strategy for therapy. In this paper, we summarize prerequisites defense systems occurrence targets drug-mediated action HCC, differences connections between other programmed deaths. We aim to theoretical basis, classical inducers research progress HCC cells, clued treatment regulating network. Further investigation specific mechanisms hepatocellular carcinoma interventions at stages will help us deepen our understanding carcinoma, with view providing new more precise preventive as well measures patients.
Language: Английский
Citations
22
Cells, Journal Year: 2022, Volume and Issue: 11(13), P. 2040 - 2040
Published: June 27, 2022
Ferroptosis, which has been widely associated with many diseases, is an iron-dependent regulated cell death characterized by intracellular lipid peroxide accumulation. It exhibits morphological, biochemical, and genetic characteristics that are unique in comparison to other types of death. The course ferroptosis can be accurately the metabolism iron, lipids, amino acids, various signal pathways. In this review, we summarize basic ferroptosis, its regulation, as well relationship between chronic diseases such cancer, nervous system metabolic inflammatory bowel diseases. Finally, describe regulatory effects food-borne active ingredients on ferroptosis.
Language: Английский
Citations
66
Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1826 - 1826
Published: April 4, 2022
Ferroptosis, an iron and reactive oxygen species (ROS)-dependent non-apoptotic type of regulated cell death, is characterized by a massive overload peroxidation polyunsaturated fatty acids (PUFAs), which finally results in death. Recent studies suggest that ferroptosis can influence carcinogenesis negatively therefore may be used as novel anti-cancer strategy. Hepatocellular carcinoma (HCC) deadly malignancy with poor chances survival the second leading cause cancer deaths worldwide. Diagnosis at already late stage general resistance to current therapies responsible for dismal outcome. As liver acts key factor metabolism, shown play important role HCC and, more importantly, hold potential eradicate HCC. In this review, we summarize knowledge have application therapy option provide overview translation clinical practice
Language: Английский
Citations
42
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2023, Volume and Issue: 1869(7), P. 166750 - 166750
Published: June 1, 2023
Language: Английский
Citations
31
Chemico-Biological Interactions, Journal Year: 2023, Volume and Issue: 384, P. 110713 - 110713
Published: Sept. 15, 2023
Language: Английский
Citations
26
Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116074 - 116074
Published: Dec. 25, 2023
Hepatocellular carcinoma (HCC) remains a major global health burden, and sorafenib, multi-kinase inhibitor, has shown effectiveness in the treatment of HCC is considered as first-line therapy for advanced HCC. However, response to sorafenib varies among patients, development drug resistance poses prevalent obstacle. Ferroptosis, newly characterized form cell death featured by iron-dependent lipid peroxidation, emerged critical player reaction The induction ferroptosis been augment anticancer benefits sorafenib. it also observed contribute resistance. This review presents comprehensive thorough analysis that elucidates intricate relationship between over recent years, aiming formulate effective therapeutic approaches liver cancer. Based on this exploration, we propose innovative strategies intended overcome via targeted modulation ferroptosis.
Language: Английский
Citations
24
Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)
Published: Jan. 10, 2024
Abstract According to statistics, the incidence of liver cancer is increasing yearly, and effective treatment imminent. For early cancer, resection surgery currently most treatment. However, does not treat disease in advanced patients, so finding a method with better prognosis necessary. In recent years, ferroptosis cuproptosis have been gradually defined, related studies proved that they show excellent results therapy cancer. Cuproptosis new form cell death, use combined inhibit production hepatocellular carcinoma cells has good development prospects worthy in-depth discussion by researchers. this review, we summarize research progress on treating analyze value immune propose potential pathways oncotherapy combination ferroptosis, which can provide background knowledge for subsequent research.
Language: Английский
Citations
14
Oncogene, Journal Year: 2023, Volume and Issue: 42(36), P. 2688 - 2700
Published: Aug. 3, 2023
Language: Английский
Citations
22