Polyunsaturated Fatty Acids Drive Lipid Peroxidation during Ferroptosis

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 804 - 804

Published: March 4, 2023

Ferroptosis is a form of regulated cell death that intricately linked to cellular metabolism. In the forefront research on ferroptosis, peroxidation polyunsaturated fatty acids has emerged as key driver oxidative damage membranes leading death. Here, we review involvement (PUFAs), monounsaturated (MUFAs), lipid remodeling enzymes and in highlighting studies revealing how using multicellular model organism Caenorhabditis elegans contributes understanding roles specific lipids mediators ferroptosis.

Language: Английский

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RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an m6A-dependent manner

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 21, 2022

Abstract Ferroptosis is a form of cell death characterized by lipid peroxidation. Previous studies have reported that knockout NF-κB activating protein (NKAP), an RNA-binding protein, increased peroxidation level in naive T cells and induced colon cancer cells. However, there was no literature the relationship between NKAP ferroptosis glioblastoma Notably, mechanism modulating still unknown. Here, we found knockdown Silencing sensitivity to inducers both vitro vivo. Exogenous overexpression promoted resistance positively regulating defense namely cystine/glutamate antiporter (SLC7A11). The regulation SLC7A11 can be weakened m 6 A methylation inhibitor cycloleucine writer METTL3. combined “RGAC” motif which exactly line with “RGACH” (R = A/G, H A/U/C) uncovered A-sequence. RNA Immunoprecipitation (RIP) Co-Immunoprecipitation (Co-IP) proved interaction on transcript. Following its binding A, recruited splicing factor proline glutamine-rich (SFPQ) recognize splice site then conducted transcription termination (TTS) event transcript retention last exon, screened RNA-sequence Mass Spectrometry (MS). In conclusion, acted as new suppressor promoting mRNA maturation.

Language: Английский

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A MOF-Based Potent Ferroptosis Inducer for Enhanced Radiotherapy of Triple Negative Breast Cancer

ACS Nano, Journal Year: 2023, Volume and Issue: 17(14), P. 13195 - 13210

Published: May 31, 2023

Radiotherapy (RT) is one of the important clinical treatments for local control triple-negative breast cancer (TNBC), but radioresistance still exists. Ferroptosis has been recognized as a natural barrier progression and represents significant role RT-mediated anticancer effects, while simultaneous activation ferroptosis defensive system during RT limits synergistic effect between ferroptosis. Herein, we engineered tumor microenvironment (TME) degradable nanohybrid with dual radiosensitization manner to combine induction high-Z based on metal-organic frameworks ferroptosis-augmented TNBC. The encapsulated l-buthionine-sulfoximine (BSO) could inhibit glutathione (GSH) biosynthesis peroxidase 4 (GPX4) inactivation break down system, delivered ferrous ions act powerful executor via triggering Fenton reaction; combination them induces potent ferroptosis, which synergize surface decorated Gold (Au) NPs-mediated improve efficacy. In vivo antitumor results revealed that significantly therapeutic efficacy antimetastasis efficiency combinational mechanism RT. This work thus demonstrated combining efficient through nanotechnology was feasible promising strategy TNBC treatment.

Language: Английский

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Regulatory pathways and drugs associated with ferroptosis in tumors

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(6)

Published: June 10, 2022

Abstract Ferroptosis is a type of cell death that depends on iron and reactive oxygen species (ROS). The accumulation lipid peroxidation primarily initiates oxidative membrane damage during ferroptosis. core molecular mechanism ferroptosis includes the regulation oxidation balance between antioxidant defense. Tumor cells usually contain large amount H 2 O , ferrous/iron ions will react with excessive in to produce hydroxyl radicals induce tumor cells. Here, we reviewed latest studies introduced tumor-related signaling pathways We paid particular attention role noncoding RNA, nanomaterials, drugs, targeted treatment using drugs for mediating process Finally, discussed currently unresolved problems future research directions prospects this emerging field. Therefore, have attempted provide reference further understanding pathogenesis proposed new targets cancer treatment.

Language: Английский

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Nanoparticle delivery of miR-21-3p sensitizes melanoma to anti-PD-1 immunotherapy by promoting ferroptosis

Journal for ImmunoTherapy of Cancer, Journal Year: 2022, Volume and Issue: 10(6), P. e004381 - e004381

Published: June 1, 2022

Background Although anti-programmed cell death protein 1 (PD-1) immunotherapy is greatly effective in melanoma treatment, low response rate and treatment resistance significantly hinder its efficacy. Tumor ferroptosis triggered by interferon (IFN)-γ that derived from tumor-infiltrating CD8 + T cells contributes to the effect of immunotherapy. However, molecular mechanism underlying IFN-γ-mediated related potentially promising therapeutic strategy warrant further clarification. MicroRNAs (miRNAs) participate execution can be delivered systemically multiple carriers, which have manifested obvious effects on cancer. Methods MiRNAs expression profile IFN-γ-driven was obtained RNA sequencing. Biochemical assays were used clarify role miR-21-3p mechanism. MiR-21-3p-loaded gold nanoparticles constructed applied analyze anti-PD-1 preclinical transplanted tumor model. Results first obtained. Then, upregulated proved facilitate potentiating lipid peroxidation. increased sensitivity directly targeting thioredoxin reductase (TXNRD1) enhance reactive oxygen species (ROS) generation. Furthermore, overexpression synergized with antibody promoting ferroptosis. More importantly, miR-21-3p-loaded constructed, systemic delivery them efficacy without prominent side mice Ultimately, ATF3 found promote transcription Conclusions MiR-21–3 p upregulation synergizes antibody. Nanoparticle miR-21–3 a approach increase effects.

Language: Английский

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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

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Ferroptosis in colorectal cancer: Potential mechanisms and effective therapeutic targets

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 153, P. 113524 - 113524

Published: Aug. 13, 2022

Colorectal cancer (CRC) is a common malignant tumor characterized by unchecked division and survival of abnormal cells in the colon or rectum with high morbidity mortality. Despite rapid development early screening methods improved therapies, prognosis CRC not satisfactory. Identification new biomarkers for detection more effective therapies are still urgent tasks current studies to achieve ideal treatment CRC. Ferroptosis recently emerged novel regulated form cell death massive accumulation iron-dependent lipid peroxidates, making it morphologically molecularly distinct from apoptosis, death, autophagy. Accumulating have shown that induction ferroptosis successfully eliminates resistant other modes death. Thus, may become direction design therapy. Although many research articles investigated possible roles CRC, study summarizes main findings, including regulators mechanisms action, available. Herein, recent literature regarding on progression were summarized, mainly focusing molecular biological vitro vivo. In particular, numerous regulators, such as SLC7A11, reactive oxygen species (ROS), glutathione (GSH), iron, discussed application ferroptosis-associated genes diagnosis was explored. addition, an outlook future barriers corresponding solutions discussed.

Language: Английский

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Radiotherapy-mediated redox homeostasis-controllable nanomedicine for enhanced ferroptosis sensitivity in tumor therapy

Acta Biomaterialia, Journal Year: 2023, Volume and Issue: 159, P. 300 - 311

Published: Jan. 13, 2023

Language: Английский

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A ferroptosis-targeting ceria anchored halloysite as orally drug delivery system for radiation colitis therapy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 22, 2023

Radiation colitis is the leading cause of diarrhea and hematochezia in pelvic radiotherapy patients. This work advances pathogenesis radiation from perspective ferroptosis. An oral Pickering emulsion stabilized with halloysite clay nanotubes to alleviate by inhibiting Ceria nanozyme grown situ on can scavenge reactive oxygen species, deferiprone was loaded into lumen relieve iron stress. These two strategies effectively inhibit lipid peroxidation rescue ferroptosis intestinal microenvironment. The play a critical role as either medicine colitis, nanocarrier that targets inflamed colon electrostatic adsorption, or an interfacial stabilizer for emulsions. ferroptosis-based strategy effective vitro vivo, providing prospective candidate protection via rational regulation specific oxidative

Language: Английский

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GPX4, ferroptosis, and diseases

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512

Published: April 3, 2024

GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.

Language: Английский

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