Emerging mechanisms and applications of ferroptosis in the treatment of resistant cancers

Biomedicine & Pharmacotherapy, Journal Year: 2020, Volume and Issue: 130, P. 110710 - 110710

Published: Sept. 16, 2020

The development of chemotherapy drugs has promoted anticancer treatment, but the effect on tumours is not clear because treatment resistance; thus, it necessary to further understand mechanism cell death explore new therapeutic targets. As a type programmed death, ferroptosis increasingly being targeted in many cancers with clinical and experimental compounds. Ferroptosis stimulated inherently high levels ferrous ions by reaction abundant polyunsaturated fatty acids inhibition antioxidant enzymes, which can overcome resistance mainly through GPX4. In this review, we focus intrinsic cellular regulators against cancer resistance, such as GPX4, NRF2 thioredoxin system. We summarize application novel compounds circumvent resistance. also introduce nanoparticles for resistant cancers. conclusion, targeting represents considerable strategy treatment.

Language: Английский

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RETRACTED ARTICLE: Circ_0008035 contributes to cell proliferation and inhibits apoptosis and ferroptosis in gastric cancer via miR-599/EIF4A1 axis

Cancer Cell International, Journal Year: 2020, Volume and Issue: 20(1)

Published: March 16, 2020

Abstract Background Currently, multiple circular RNAs (circRNAs) have been verified to act as essential regulators in the progression of gastric cancer (GC). We aimed investigate role circ_0008035 GC progression. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized measure expression and miR-599. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2- H -tetrazolium bromide (MTT) assay employed evaluate cell proliferation ferroptosis. Western blot performed levels cyclin D1, proliferating nuclear antigen (PCNA) eukaryotic initiation factor 4A1 (EIF4A1). Flow cytometry analysis conducted assess apoptosis. The iron accumulation, lipid peroxidation mitochondrial membrane potential were examined by relevant kits. Dual-luciferase reporter determine targeting relationship between miR-599 or EIF4A1. A murine xenograft model established function vivo. Results Circ_0008035 up-regulated tissues cells. Silencing repressed induced apoptosis ferroptosis acted a sponge effects knockdown on proliferation, abolished inhibition. EIF4A1 confirmed be target gene inhibited Moreover, suppressive deficiency could restored Additionally, circ-0008035 hampered tumorigenesis Conclusion promoted growth up-regulating through sponging

Language: Английский

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Ferroptosis: Biochemistry and Biology in Cancers

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: April 1, 2021

The challenge of eradicating cancer is that cells possess diverse mechanisms to protect themselves from clinical strategies. Recently, ferroptosis has been shown exhibit appreciable anti-tumor activity could be harnessed for therapy in the future. Ferroptosis an iron-dependent form regulated cell death characterized by oxidization polyunsaturated fatty acids (PUFAs) and accumulation lipid peroxides. closely correlated with numerous biological processes, such as amino acid metabolism, glutathione iron well key regulators including GPX4, FSP1, NRF2, p53. Although involved killing various cells, multiple aspects this phenomenon remain unresolved. In review, we summarize biochemistry biology cancers discuss potential ferroptosis, which might pave way guiding therapeutics.

Language: Английский

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Emerging Mechanisms and Disease Implications of Ferroptosis: Potential Applications of Natural Products

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 18, 2022

Ferroptosis, a newly discovered form of regulatory cell death (RCD), has been demonstrated to be distinct from other types RCD, such as apoptosis, necroptosis, and autophagy. Ferroptosis is characterized by iron-dependent lipid peroxidation oxidative perturbation, inhibited iron chelators lipophilic antioxidants. This process regulated specific pathways implicated in diverse biological contexts, mainly including homeostasis, metabolism, glutathione metabolism. A large body evidence suggests that ferroptosis interrelated with various physiological pathological processes, tumor progression (neuro)degenerative diseases, hepatic renal failure. There an urgent need for the discovery novel effective ferroptosis-modulating compounds, even though some experimental reagents approved clinical drugs have well documented anti- or pro-ferroptotic properties. review outlines recent advances molecular mechanisms ferroptotic discusses its multiple roles pathophysiological contexts. Furthermore, we summarize chemical compounds natural products, act inducers inhibitors prevention treatment diseases. Herein, it particularly highlighted products show promising prospects ferroptosis-associated (adjuvant) therapy unique advantages having components, biotargets slight side effects.

Language: Английский

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Targeting Ferroptosis Pathway to Combat Therapy Resistance and Metastasis of Cancer

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: June 30, 2022

Ferroptosis is an iron-dependent regulated form of cell death caused by excessive lipid peroxidation. This differed from known forms in morphological and biochemical features such as apoptosis, necrosis, autophagy. Cancer cells require higher levels iron to survive, which makes them highly susceptible ferroptosis. Therefore, it was found be closely related the progression, treatment response, metastasis various cancer types. Numerous studies have that ferroptosis pathway drug resistance cancer. Some reduce their susceptibility downregulating pathway, resulting anticancer therapy. Induction restores sensitivity drug-resistant standard treatments. are resistant conventional therapies or a high propensity metastasize might particularly biological processes cellular components, epithelial–mesenchymal transition (EMT) noncoding RNAs, can influence regulating targeting may help suppress metastasis. Those progresses revealed importance cancer, In order provide detailed molecular mechanisms therapy strategies overcome these barriers not fully understood, we described key its interaction with signaling pathways Furthermore, summarized for reversing targeted therapy, chemotherapy, radiotherapy, immunotherapy inhibiting modulating Understanding comprehensive regulatory new insights enhance efficacy drugs, resistance, inhibit

Language: Английский

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Ferroptosis and its Role in Gastric Cancer

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: June 30, 2022

Gastric cancer (GC) is the fifth most common and third leading cause of cancer-related deaths worldwide. Currently, surgery treatment choice for GC. However, associated expenses post-surgical pain impose a huge burden on these patients. Furthermore, disease recurrence also very in GC patients, thus necessitating discovery development other potential options. A growing body knowledge about ferroptosis different types provides new perspective therapeutics. Ferroptosis an iron-dependent form cell death. It characterized by intracellular lipid peroxide accumulation redox imbalance. In this review, we summarized current findings regulation We tackled action drugs genes inducing treating solving drug resistance. explored relationship between tumor microenvironment Finally, discussed areas future studies role to accelerate clinical utility induction as strategy

Language: Английский

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The epigenetic regulatory mechanisms of ferroptosis and its implications for biological processes and diseases

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 22, 2023

Abstract Ferroptosis is a form of regulated cell death triggered by the iron‐dependent peroxidation phospholipids. Interactions iron and lipid metabolism factors jointly promote ferroptosis. has been demonstrated to be involved in development various diseases, such as tumors degenerative diseases (e.g., aortic dissection), targeting ferroptosis expected an effective strategy for treatment these diseases. Recent studies have shown that regulation affected multiple mechanisms, including genetics, epigenetics, posttranscriptional modifications, protein posttranslational modifications. Epigenetic changes garnered considerable attention due their importance regulating biological processes potential druggability. There many on epigenetic ferroptosis, histone modifications acetylation methylation), DNA methylation, noncoding RNAs miRNAs, circRNAs, lncRNAs). In this review, we summarize recent advances research mechanisms with description RNA N 6 ‐methyladenosine (m A) methylation included, ferroptosis‐related which provides reference clinical application regulators related

Language: Английский

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Glutaminases regulate glutathione and oxidative stress in cancer

Archives of Toxicology, Journal Year: 2020, Volume and Issue: 94(8), P. 2603 - 2623

Published: July 18, 2020

Language: Английский

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Glutaminase in microglia: A novel regulator of neuroinflammation

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 92, P. 139 - 156

Published: Dec. 3, 2020

Neuroinflammation is the inflammatory responses that are involved in pathogenesis of most neurological disorders. Glutaminase (GLS) enzyme catalyzes hydrolysis glutamine to produce glutamate. Besides its well-known role cellular metabolism and excitatory neurotransmission, GLS has recently been increasingly noticed be up-regulated activated microglia under pathological conditions. Furthermore, overexpression induces microglial activation, extracellular vesicle secretion, neuroinflammatory microenvironment formation, which, compromised by inhibitors vitro vivo. These results indicate more complicated implications brain disease etiology than what previously known. In this review, we introduce isoforms, expression patterns body brain, expression/activities regulation. Next, discuss metabolic neurotransmission functions GLS. Afterwards, summarize recent findings GLS-mediated activation pro-inflammatory turns, neuroinflammation. Lastly, provide a comprehensive discussion for involvement various disorders, indicating as promising target treat these diseases.

Language: Английский

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Natural Products as Inducers of Non-Canonical Cell Death: A Weapon against Cancer

Cancers, Journal Year: 2021, Volume and Issue: 13(2), P. 304 - 304

Published: Jan. 15, 2021

Apoptosis has been considered the main mechanism induced by cancer chemotherapeutic drugs for a long time. This paradigm is currently evolving and changing, as increasing evidence pointed out that antitumor agents could trigger various non-canonical or non-apoptotic cell death types. A considerable number of derive from natural sources, both in their naturally occurring form synthetic derivatives. Therefore, it not surprising several compounds have explored ability to induce death. The aim this review highlight potential effects products ferroptosis, necroptosis, pyroptosis inducers. Natural proven be promising inducers, capable overcoming cells resistance apoptosis. However, discussed review, they often lack full characterization activity together with an in-depth investigation toxicological profile.

Language: Английский

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