Ferroptosis: principles and significance in health and disease

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Language: Английский

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TRIB3 inhibition by palbociclib sensitizes prostate cancer to ferroptosis via downregulating SOX2/SLC7A11 expression

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 3, 2024

Language: Английский

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Microfluidic fabrication of lipid nanoparticles for co-delivery of siRNA and hydroxychloroquine: An engineered theranostic platform for enhanced breast cancer treatment

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160172 - 160172

Published: Feb. 1, 2025

Language: Английский

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RSL3-loaded nanoparticles amplify the therapeutic potential of cold atmospheric plasma

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 24, 2025

Cold atmospheric plasma (CAP) has exhibited exciting potential for cancer treatment. Reactive oxygen and nitrogen species (RONS), the primary constituents in CAP, contribute to cell death by elevating oxidative stress cells. However, several intrinsic cellular antioxidant defense systems exist, such as glutathione peroxidase 4 (GPX4) enzyme, which dampens cell-killing efficacy of CAP. RAS-selective lethal 3 (RSL3), also known a ferroptosis inducer, is synthetic GPX4 inhibitor. Therefore, we hypothesized that RSL3 can amplify CAP-induced inhibition GPX4. In this study, showed loaded poly (ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG) nanoparticles enhance deaths 4T1 tumor Furthermore, combination CAP promoted immunogenic (ICD), induced dendritic (DC) maturation, macrophage polarization, initiating tumor-specific T-cell mediated immune responses against tumors. For vivo application, RSL3@NP was co-delivered with via injectable Pluronic hydrogel. 4T1-bearing mice, hydrogel-mediated delivery RSL3-loaded effectively elicit potent anti-tumor inhibit growth.

Language: Английский

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Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 3, 2025

Aberrant lipid metabolism is a well-recognized hallmark of cancer. Notably, breast cancer (BC) arises from lipid-rich microenvironment and depends significantly on metabolic reprogramming to fulfill its developmental requirements. In this review, we revisit the pivotal role in BC, underscoring impact progression tumor microenvironment. Firstly, delineate overall landscape highlighting roles patient prognosis. Given that lipids can also act as signaling molecules, next describe exchanges between BC cells other cellular components Additionally, summarize therapeutic potential targeting aspects processes, lipid-related transcription factors immunotherapy BC. Finally, discuss possibilities problems associated with clinical applications lipid‑targeted therapy propose new research directions advances spatiotemporal multi-omics.

Language: Английский

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Molecular characterization of colorectal cancer (CRC) using next generation sequencing (NGS) in bridging the gap between research and clinical practice: from biomarker discovery to clinical implementation

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 6, 2025

Colorectal cancer (CRC) is the second most common in men and third females, a heterogeneous disease involving multistep mechanisms that represents 10% of all cancers globally. This study investigates gene mutation profiling CRC using Next-Generation sequencing machine. Formalin-fixed paraffin-embedded tissues 30 patients were retrieved reviewed. DNA was isolated from selected tissues. Desirable quality check Qubit Nanoquant machine done, desirable libraries prepared loaded into sequencer for sequencing. Using Illumina BaseSpace Variant interpreter, generated FastQ data treated annotation, alignment, mapping with reference genome. Sequencing-runs Phred-score ≥ as runs. Finally, variants validated on NCBI-dsSNP Ensembl databases clinical consequence interpretations. Overall, patient distribution consists 12(40%) females 18 (60%) males mean age (53.2 + 5.3). TNM stage-3: 53.3% (15/30) least Stage-4: 20%(6/30) respectively. 73.3%: (22/30) completed sequencing, 552 mutations 29 genes 12 chromosomes detected. The upregulated are KIT:68(12.3%), FGFR4:61(11.1%), EGFR:60(10.9%), ALK:53(9.6%), DCUN1D1:41(7.4%), PDGFR:40(7.2%), KRAS:33(6.0%), CDK4:27(4.9%), FGFR3:26(4.7%), MTOR:14(2.6), while NRAS, CDK6, PIK3CA, RET each has 13(2.4%) apiece. Chromosomes 4:134/55(24.2%), chr7:84/552(15.2%), chr12:71/552(12.9%), chr5:64/552(11.6%), chr2:61/552(11.1%), chr3:54/552(9.8%), chr1:43/552(7.8%) involved chromosomes. Nine (APC, ALK, KRAS, IDH1, FGFR1, ERBB2, ESR1) identified pathogenic-causing CRC. first NGS-based molecular FFPE-CRC hospital-USM showed nine crucial pathogenic variants.

Language: Английский

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Engineered lung cell targeting and SLC7A11 siRNA expressing bacterial extracellular vesicles impair the progression of none‐small cell lung cancer

Bioengineering & Translational Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Non‐small cell lung cancer (NSCLC) presents significant therapeutic challenges, often characterized by aggressive proliferation and metastasis. This study investigates the role of SLC7A11, a ferroptosis‐related gene, in NSCLC progression potential engineered bacterial extracellular vesicles (BEVs) expressing SLC7A11‐targeting siRNA as strategy. Using TCGA GEO databases, we identified that SLC7A11 was significantly upregulated tissues. Functional assays demonstrated knockdown lines (NCI‐H2122 NCI‐H647) via qPCR, Western blot, immunofluorescence resulted impaired proliferation, migration, invasion abilities. In vivo xenograft models further revealed inhibited tumor growth metastasis, corroborated histological analyses. To enhance targeted delivery siRNA, BEVs with targeting peptide, verifying their structure function through transmission electron microscopy (TEM) nanoparticle tracking analysis (NTA). toxicity assessments indicated safety for these bioengineered vesicles. Importantly, treatment BEVs‐LCTP‐siSLC7A11 not only tumorigenesis but also activated ferroptosis pathways, evidenced altered expression levels transferrin metastatic Our findings suggest promising approach to inhibit while activating ferroptosis, offering insights into novel strategies against cancer.

Language: Английский

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Design, synthesis, and biological evaluation of novel CDK4/6 and BRD4 dual inhibitors for treatment of KRAS-mutant NSCLC

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117685 - 117685

Published: April 1, 2025

Language: Английский

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A combination of a TLR7/8 agonist and an epigenetic inhibitor suppresses triple-negative breast cancer through triggering anti-tumor immune

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 29, 2024

Abstract Background Combination therapy involving immune checkpoint blockade (ICB) and other drugs is a potential strategy for converting immune-cold tumors into immune-hot to benefit from immunotherapy. To achieve drug synergy, we developed homologous cancer cell membrane vesicle (CM)-coated metal-organic framework (MOF) nanodelivery platform the codelivery of TLR7/8 agonist with an epigenetic inhibitor. Methods A novel biomimetic system (MCM@UN) was constructed by MOF nanoparticles UiO-66 loading bromodomain-containing protein 4 (BRD4) inhibitor then coated vesicles cells that embedding 18 C lipid tail 3M-052 (M). The antitumor ability tumor suppressive effect MCM@UN were evaluated in mouse model triple-negative breast (TNBC) vitro. microenvironment analyzed multicolor immunofluorescence staining. Results In vitro vivo data showed specifically targeted TNBC superior free terms growth inhibition activity. mechanism, blocked BRD4 PD-L1 prompt dying disintegrate expose antigens. disintegrated released damage-associated molecular patterns (DAMPs), recruited dendritic (DCs) efficiently activate CD8 + T mediate effective long-lasting immunity. addition, on enhanced lymphocytes infiltration immunogenic death decreased regulatory T-cells (Tregs). On clinical specimens, found mature DCs infiltrating tissues patients negatively correlated expression BRD4, which consistent result animal model. Conclusion remodeled inhibit malignant behaviors TNBC.

Language: Английский

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Targeting ferroptosis as a potential prevention and treatment strategy for aging-related diseases

Pharmacological Research, Journal Year: 2024, Volume and Issue: 208, P. 107370 - 107370

Published: Aug. 23, 2024

Ferroptosis, an emerging paradigm of programmed cellular necrosis posited in recent years, manifests across a spectrum maladies with profound implications for human well-being. Numerous investigations substantiate that modulating ferroptosis, whether through inhibition or augmentation, plays pivotal role the etiology and control numerous age-related afflictions, encompassing neurological, circulatory, respiratory, other disorders. This paper not only summarizes regulatory mechanisms but also discusses impact ferroptosis on biological processes aging its diseases. Furthermore, it scrutinizes therapeutic strides addressing aging-related conditions modulation ferroptosis. The consolidates existing knowledge potential applications ferroptosis-related pharmacotherapies envisages translational prospects ferroptosis-targeted interventions clinical paradigms.

Language: Английский

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