Tangeretin alleviates sepsis-induced acute lung injury by inhibiting ferroptosis of macrophage via Nrf2 signaling pathway DOI Creative Commons
Hui Zhang, Yan Wang, Shenghua Wang

и другие.

Chinese Medicine, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 15, 2025

Abstract Background Sepsis-induced acute lung injury (ALI) is a severe clinical condition accompanied with high mortality. Tangeretin, which widely found in citrus fruits, has been reported to exert antioxidant and anti-inflammatory properties. However, whether tangeretin protects against sepsis-induced ALI the potential mechanisms remain unclear. Methods We established an model via intraperitoneally injected 5 mg/kg lipopolysaccharides (LPS) for 12 h. Tangeretin was applied 30 min before LPS treatment. Dexamethasone (Dex) used as positive control. Hematoxylin eosin (HE) staining protein content bronchoalveolar lavage fluid (BALF) were determined detect degree of injury. RNA-seq also explore effect on ALI. In vitro, RAW264.7 treated Nrf2 siRNA, expression ferroptosis-associated biomarkers, including glutathione peroxidase 4 (GPX4) prostaglandin-endoperoxide synthase 2 (PTGS2) assessed. Glutathione (GSH), malondialdehyde (MDA) levels, reactive oxygen species (ROS) inflammatory factors both vivo vitro. Furthermore, mice inhibitor (ML385) verify mechanism inhibiting ferroptosis. Data analyzed using one way analysis variance or two-tailed unpaired t tests. Results Our study demonstrated that significantly alleviated injury, reversed LPS-induced reduction GPX4 GSH, mitigates elevation PTGS2 MDA levels. reduced 4-HNE iron Besides, levels LPS-stimulated IL-6, IL-1β TNF-α decreased by tangeretin. bioinformatics inhibited response. Mechanistically, we identified GPX4-dependent lipid peroxidation through activation Nrf2. The silence abolished inhibitory oxidative stress, response ferroptosis cells. Additionally, all protective effects inhibitor-treated mice. Conclusion critical contributing promising therapeutic candidate, effectively upregulating signaling pathway.

Язык: Английский

Regulated cell death in myocardial ischemia–reperfusion injury DOI
Q. Xiang, Xin Yi,

Xue‐Hai Zhu

и другие.

Trends in Endocrinology and Metabolism, Год журнала: 2023, Номер 35(3), С. 219 - 234

Опубликована: Ноя. 17, 2023

Язык: Английский

Процитировано

152
Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers DOI Creative Commons
Yuanfang Li, Baiwei Zhao,

Juzheng Peng

и другие.

Drug Resistance Updates, Год журнала: 2024, Номер 73, С. 101042 - 101042

Опубликована: Янв. 4, 2024

Drug resistance in cancer remains a major challenge oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as critical player development drug cells. This comprehensive review explores intricate relationship between NF-κB and cancer. We delve into molecular mechanisms through which activation contributes to against chemotherapeutic agents, targeted therapies, immunotherapies. Additionally, we discuss potential strategies overcome this by targeting signaling, such small molecule inhibitors combination therapies. Understanding multifaceted interactions is crucial for more effective strategies. By dissecting complex network NF-κB, hope shed light on novel therapeutic approaches that can enhance outcomes, ultimately improving prognosis patients. aims provide overview current state knowledge its role resistance, offering insights may guide future research interventions fight

Язык: Английский

Процитировано

37
Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer DOI Creative Commons
Hua Su, Chao Peng, Yang Liu

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Март 18, 2024

The global challenge posed by cancer, marked rising incidence and mortality rates, underscores the urgency for innovative therapeutic approaches. PI3K/Akt signaling pathway, frequently amplified in various cancers, is central regulating essential cellular processes. Its dysregulation, often stemming from genetic mutations, significantly contributes to cancer initiation, progression, resistance therapy. Concurrently, ferroptosis, a recently discovered form of regulated cell death characterized iron-dependent processes lipid reactive oxygen species buildup, holds implications diseases, including cancer. Exploring interplay between dysregulated pathway ferroptosis unveils potential insights into molecular mechanisms driving or inhibiting ferroptotic cells. Evidence suggests that may sensitize cells induction, offering promising strategy overcome drug resistance. This review aims provide comprehensive exploration this interplay, shedding light on disrupting enhance as an alternative route inducing improving treatment outcomes.

Язык: Английский

Процитировано

30
Interplay of Ferroptosis and Cuproptosis in Cancer: Dissecting Metal-Driven Mechanisms for Therapeutic Potentials DOI Open Access
Jinjiang Wang, Jiaxi Li, Jiao Liu

и другие.

Cancers, Год журнала: 2024, Номер 16(3), С. 512 - 512

Опубликована: Янв. 24, 2024

Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, oxidative stress. The emergence of ferroptosis cuproptosis as distinct forms non-apoptotic death has heightened their significance, particularly connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence cuproptosis. Studies reveal a link between accumulation induction. This interconnected relationship presents promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing toxicity iron clinical settings becomes crucial. Simultaneous targeting cuproptosis, exemplified combination sorafenib elesclomol-Cu, represents an intriguing approach. Strategies mitochondria further enhance precision approaches, providing hope improving treatment outcomes drug-resistant cancers. Moreover, chelators copper-lowering agents established therapeutic modalities exhibits synergy that holds promise augmentation anti-tumor efficacy malignancies. review elaborates on complex interplay underlying mechanisms, explores potential druggable targets both research settings.

Язык: Английский

Процитировано

24
Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors DOI Creative Commons

Carolina Punziano,

Silvia Trombetti, Elena Cesaro

и другие.

Antioxidants, Год журнала: 2024, Номер 13(3), С. 298 - 298

Опубликована: Фев. 28, 2024

Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, ischemia–reperfusion injuries. linked iron accumulation, eliciting dysfunction antioxidant systems, which favor the production lipid peroxides, membrane damage, ultimately, death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against excess and/or lipid-derived ROS. Here, we discuss interaction between metabolic particular focus on transcription factors implicated in regulation ferroptosis, either as triggers peroxidation or defense pathways.

Язык: Английский

Процитировано

21
RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel DOI Creative Commons

Jialin Yuan,

Cong Liu,

Chengwei Jiang

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 11, 2025

Chemotherapy resistance in triple-negative breast cancer (TNBC) leads to poor therapeutic effects and a prognosis. Given that paclitaxel-based chemotherapy is the main treatment method for TNBC, enhancing its chemosensitivity has been research focus. Induced ferroptosis of tumour cells proven increase chemosensitivity, but ability sensitize TNBC paclitaxel (PTX) unknown. In our experiments, measurements viability proliferation validated synergistic effect PTX combined with RSL3 on cells. The accumulation intracellular Fe2+ lipid reactive oxygen species, as well expression malondialdehyde, illustrated enhanced by inducing ferroptosis. Through transcriptome sequencing, series differentially expressed genes were identified, which cytokines, such CXCLs, was significantly increased group, combination therapy enriched mainly NFκB signalling pathway. subsequent validation use NF-κB inhibitor BAY11-7082 reversed inhibitory cell activity. xenograft immunodeficient mouse model, vivo further verified. Our both vitro, activating pathway, thereby increasing PTX. This study provides new insights improving efficacy strategies.

Язык: Английский

Процитировано

4
SPHK1 enhances olaparib resistance in ovarian cancer through the NFκB/NRF2/ferroptosis pathway DOI Creative Commons

Kai Teng,

Hanlin Ma,

Panpan Gai

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 28, 2025

Abstract PARPis resistance is a challenge in the treatment of ovarian cancer. To investigate potential mechanism involved olaparib cancer, high-throughput sequencing was performed on olaparib-resistant SKOV3 cell line named SK/Ola. SPHK1 upregulated SK/Ola cells and related to PFS OS cancer patients. However, effect sensitivity were obscure. In this study, we found that promoted resistance. While, knockdown inhibitor (PF-543 hydrochloride, PF-543 article) enhanced cells. mechanism, activated NF-κB pathway through promoting p-IκBα degradation. Moreover, inhibited, but ferroptosis OC Further investigation revealed p65, which turn transcriptionally regulated NRF2 inhibit Functionally, p65 attenuated PF-543-induced ferroptosis, rescued by inducer erastin RSL3. We conclude inhibition triggers restricting NF-κB-activated transcription, thereby enhancing vivo experiments also confirmed increased sensitivity. A combination inhibitors may provide therapeutic strategy for

Язык: Английский

Процитировано

4
Hyperoxia-activated Nrf2 regulates ferroptosis in intestinal epithelial cells and intervenes in inflammatory reaction through COX-2/PGE2/EP2 pathway DOI Creative Commons
Yanping Liu,

Tianming Li,

Changping Niu

и другие.

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Янв. 3, 2025

Язык: Английский

Процитировано

3
Scutellarein alleviates chronic obstructive pulmonary disease through inhibition of ferroptosis by chelating iron and interacting with arachidonate 15‐lipoxygenase DOI
Lu Liu, Yunsen Zhang, Lun Wang

и другие.

Phytotherapy Research, Год журнала: 2023, Номер 37(10), С. 4587 - 4606

Опубликована: Июнь 24, 2023

Abstract Ferroptosis, an iron‐dependent cell death characterized by lethal lipid peroxidation, is involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Therefore, ferroptosis inhibition represents attractive strategy for COPD therapy. Herein, we identified natural flavonoid scutellarein as a potent inhibitor the first time, and its underlying mechanisms of COPD. In vitro, anti‐ferroptotic activity was investigated through CCK8, real‐time quantitative polymerase chain reaction (RT‐qPCR), Western blotting, flow cytometry, transmission electron microscope (TEM). vivo, induced lipopolysaccharide (LPS)/cigarette smoke (CS) assessed changes histopathological, inflammatory, ferroptotic markers. The were RNA‐sequencing (RNA‐seq), electrospray ionization mass spectra (ESI‐MS), local surface plasmon resonance (LSPR), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), molecular dynamics. Our results showed that significantly inhibited Ras‐selective small molecule (RSL)‐3‐induced mitochondria injury BEAS‐2B cells, ameliorated LPS/CS‐induced mice. Furthermore, also repressed RSL‐3‐ or GPX4 down‐regulation, overactivation Nrf2/HO‐1 JNK/p38 pathways. Mechanistically, Fe 2+ elevation directly chelating . Moreover, bound to peroxidizing enzyme arachidonate 15‐lipoxygenase (ALOX15), which resulted unstable state catalysis‐related cluster. Additionally, ALOX15 overexpression partially abolished scutellarein‐mediated activity. findings revealed alleviated inhibiting via interacting with ALOX15, highlighted candidate treatment other ferroptosis‐related diseases.

Язык: Английский

Процитировано

31
Effects of DNA, RNA, and Protein Methylation on the Regulation of Ferroptosis DOI Creative Commons

X R Wang,

Xianghai Kong,

Xin Feng

и другие.

International Journal of Biological Sciences, Год журнала: 2023, Номер 19(11), С. 3558 - 3575

Опубликована: Янв. 1, 2023

Ferroptosis is a form of programmed cell death characterized by elevated intracellular ferrous ion levels and increased lipid peroxidation.Since its discovery characterization in 2012, considerable progress has been made understanding the regulatory mechanisms pathophysiological functions ferroptosis.Recent findings suggest that numerous organ injuries (e.g., ischemia/reperfusion injury) degenerative pathologies aortic dissection neurodegenerative disease) are driven ferroptosis.Conversely, insufficient ferroptosis linked to tumorigenesis.Furthermore, recent study revealed effect on hematopoietic stem cells under physiological conditions.The identified date include mainly iron metabolism, such as transport ferritinophagy, redox systems, glutathione peroxidase 4 (GPX4)-glutathione (GSH), ferroptosis-suppressor-protein 1 (FSP1)-CoQ10, FSP1-vitamin K (VK), dihydroorotate dehydrogenase (DHODH)-CoQ, GTP cyclohydrolase (GCH1)-tetrahydrobiopterin (BH4).Recently, an increasing number studies have demonstrated important role played epigenetic mechanisms, especially DNA, RNA, protein methylation, ferroptosis.In this review, we provide critical analysis molecular networks date, with focus methylation.Furthermore, discuss some debated unanswered questions should be foci future research field.

Язык: Английский

Процитировано

30