Bee Pollen Potential to Modulate Ferroptosis: Phytochemical Insights for Age-Related Diseases DOI Creative Commons

Rachid Kacemi,

María G. Campos

Antioxidants, Год журнала: 2025, Номер 14(3), С. 265 - 265

Опубликована: Фев. 25, 2025

Bee pollen (BP) is one of the richest known natural resources micronutrients and bioactive phytochemicals. Some captivating bioactivities BP compounds, although being largely investigated for latter as individual molecules, remain very scarcely or completely uninvestigated in bee a whole product. Among most intriguing these bioactivities, we identified ferroptosis major one. Ferroptosis, recently discovered form cell death (connecting oxidative stress inflammation), complex pathophysiological process crucial perplexing events current challenging human diseases such cancer, neurodegeneration, general aging diseases. Many compounds were found to intricately modulate depending on cellular context by inducing this mechanism malignant cells preventing it non-malignant cells. Since research both fields, i.e., ferroptosis, still recent, deemed necessary undertake review figure out extent potential modulating mechanisms. Our proved that wide range (polyphenols, phenolamides, carotenoids, vitamins, minerals, others) substantially diverse Accordingly, phytochemicals nutrients showed interesting preclinical studies lead ferroptosis-mediated outcomes important processes, including many aging-related disorders. One paramount challenges be resolved determine how different act biological contexts, either through synergistic antagonistic behaviors. We hope our work constitutes valuable incentive future investigations promising relevant avenue.

Язык: Английский

SLC7A11 as a Gateway of Metabolic Perturbation and Ferroptosis Vulnerability in Cancer DOI Creative Commons
Jaewang Lee, Jong‐Lyel Roh

Antioxidants, Год журнала: 2022, Номер 11(12), С. 2444 - 2444

Опубликована: Дек. 11, 2022

SLC7A11 is a cell transmembrane protein composing the light chain of system xc-, transporting extracellular cystine into cells for cysteine production and GSH biosynthesis. critical gateway redox homeostasis by maintaining cellular levels that counter oxidative stress suppress ferroptosis. overexpressed in various human cancers regulates tumor development, proliferation, metastasis, microenvironment, treatment resistance. Upregulation needed to adapt high microenvironments maintain homeostasis. High basal ROS dependences cancer render them vulnerable further stress. Therefore, cyst(e)ine depletion may be an effective new strategy treatment. However, effectiveness inhibitors or cyst(e)inase has been established many preclinical studies but not reached stage clinical trials patients. A better understanding functions regulating interacting with redox-active proteins their substrates could promising this review intends understand role antioxidant signaling, regulators bioavailability cancer, linking signaling metabolism targeting novel therapeutics.

Язык: Английский

Процитировано

84
GPX4, ferroptosis, and diseases DOI Open Access

Wangzheqi Zhang,

Yang Liu,

Liao Yan

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116512 - 116512

Опубликована: Апрель 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.

Язык: Английский

Процитировано

51
Resveratrol reduces ROS-induced ferroptosis by activating SIRT3 and compensating the GSH/GPX4 pathway DOI Creative Commons
Xingjie Wang, Tianli Shen, Jie Lian

и другие.

Molecular Medicine, Год журнала: 2023, Номер 29(1)

Опубликована: Окт. 19, 2023

Intestinal ischemia-reperfusion injury occurs in acute intestinal obstruction, intussusception, mesenteric artery embolism, and other diseases can lead to local necrosis, distant organ involvement, or systemic reactions, with high morbidity mortality. Ferroptosis plays a crucial role injury, inhibition of ferroptosis may provide new approaches for treating the disease. SIRT3 protects cells from oxidative stress be involved process ferroptosis. We hypothesized that resveratrol, an agonist SIRT3, could ameliorate by compensating GSH/GPX4 pathway.Intestinal (I/R) Caco-2 hypoxia-reoxygenation models were established. Transmission electron microscopy was used assess mitochondrial function; Chiu's score evaluate degree mucosal based on HE staining; Western blot detect SIRT3/FoxO3a pathway, tight junction proteins ferroptosis-related protein expression. Sirt3-/- C57, shSIRT3-Caco-2 siFoxO3a-Caco-2 C11-BODIPY lipid peroxide cells; FD4 IFABP permeability; MitoSOX ROS levels; MitoTracker immunofluorescence colocalization levels.In I/R model, mainly during reperfusion period leads through pathway. Resveratrol reduce activating SIRT3. In mice, more underwent ferroptosis, severe, resveratrol lost ability injury. addition, increased RSL3-induced sensitivity vitro. presence shSIRT3 RSL3 alone, but not Furthermore, might activate increase expression SOD2 catalase, inhibit generation, thus reducing peroxidation ferroptosis.To date, this is first study show ameliorates increasing LPO production, pathway inhibiting increases reduces production LPO, compensates inhibits

Язык: Английский

Процитировано

45
Curcumin suppresses colorectal cancer by induction of ferroptosis via regulation of p53 and solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 signaling axis DOI

Tianqi Ming,

Jiarong Lei,

Yu‐Hui Peng

и другие.

Phytotherapy Research, Год журнала: 2024, Номер 38(8), С. 3954 - 3972

Опубликована: Июнь 4, 2024

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on CRC. The efficacies CUR malignant phenotype CRC cells were determined 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, clonogenic assays. effects evaluated transmission electron microscopy, lactate dehydrogenase release assay, Fe

Язык: Английский

Процитировано

27
Ferroptosis role in complexity of cell death: unrevealing mechanisms in Parkinson’s disease and therapeutic approaches DOI
Anupam Awasthi,

Kousik Maparu,

Shamsher Singh

и другие.

Inflammopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Язык: Английский

Процитировано

4
Susceptibility of cervical cancer to dihydroartemisinin-induced ferritinophagy-dependent ferroptosis DOI Creative Commons
Hanqiang Shi, Lie Xiong, Guang Yan

и другие.

Frontiers in Molecular Biosciences, Год журнала: 2023, Номер 10

Опубликована: Март 31, 2023

The clinical therapeutics of cervical cancer is limited due to the drug resistance and metastasis tumor. As a novel target for antitumor therapy, ferroptosis deemed be more susceptible those cells with apoptosis chemotherapy. Dihydroartemisinin (DHA), primary active metabolites artemisinin its derivatives, has exhibited variety anticancer properties low toxicity. However, role DHA in remained unclear. Here, we showed that could time-dependently dose-dependently inhibit proliferation cells, which alleviated by inhibitors rather than apoptosis. Further investigation confirmed treatment initiated ferroptosis, as evidenced accumulation reactive oxygen species (ROS), malondialdehyde (MDA) liquid peroxidation (LPO) levels simultaneously depletion glutathione peroxidase 4 (GPX4) (GSH). Moreover, nuclear receptor coactivator (NCOA4)-mediated ferritinophagy was also induced leading subsequent increases intracellular labile iron pool (LIP), exacerbated Fenton reaction resulting excessive ROS production, enhanced ferroptosis. Among them, unexpectedly found heme oxygenase-1 (HO-1) played an antioxidant DHA-induced cell death. In addition, results synergy analysis combination doxorubicin (DOX) emerged highly synergistic lethal effect related Overall, our data revealed molecular mechanisms triggered ferritinophagy-dependent sensitized DOX cancer, may provide avenues future therapy development.

Язык: Английский

Процитировано

25
Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis DOI Creative Commons

Xiangying Yan,

Yudong Liu,

Congchong Li

и другие.

Cancer Cell International, Год журнала: 2023, Номер 23(1)

Опубликована: Июнь 6, 2023

Abstract Background Malignant transformation from hepatic fibrosis to carcinogenesis may be a therapeutic target for hepatocellular carcinoma (HCC). The aim of this study was evaluate anti-cancer efficacy Pien-Tze-Huang (PZH), and investigate the underlying mechanisms by integrating transcriptional regulatory network analysis experimental validation. Methods A diethylnitrosamine (DEN)-induced HCC model in rats established used PZH. After detecting transcriptomic profiling, “disease-related gene–drug effective target” interaction constructed, candidate targets PZH against malignant were identified verified vitro. Results effectively alleviated pathological changes cirrhosis, inhibited tumor formation growth DEN-induced rats. Additionally, administration reduced levels various function-related serological indicators significantly. Mechanically, ferroptosis-related SLC7A11-GSH-GPX4 axis might one potential HCC. Especially, high SLC7A11 expression associated with poor prognosis patients. Experimentally, markedly increased trivalent iron ferrous ion, suppressed GPX4 proteins, GSH/GSSG ratio liver tissues Conclusions Our data offer an evidence that improve microenvironment prevent occurrence through promoting ferroptosis cells via inhibiting axis, implying drug prevention treatment at early stage.

Язык: Английский

Процитировано

23
Progress of Ferroptosis in Ischemic Stroke and Therapeutic Targets DOI Creative Commons
Xinjuan Tian, Xiang Li, Mengtian Pan

и другие.

Cellular and Molecular Neurobiology, Год журнала: 2024, Номер 44(1)

Опубликована: Фев. 23, 2024

Ferroptosis is an iron-dependent form of programmed cell death (PCD) and ischemic stroke (IS) has been confirmed to be closely related ferroptosis. The mechanisms ferroptosis were summarized into three interrelated aspects: iron metabolism, lipid peroxide as well glutathione amino acid metabolism. What's more, the causal relationship between IS elucidated by several processes. disruption blood-brain barrier, release excitatory acids, inflammatory response after all lead disorder metabolism antioxidant system. Based on these statements, we reviewed reported effects compounds drugs treating modulating key molecules in Through detailed analysis roles molecules, have also more clearly demonstrated essential effect occurrence so provide new targets ideas for therapeutic IS.

Язык: Английский

Процитировано

15
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

15
Glutathione Depletion and Stalwart Anticancer Activity of Metallotherapeutics Inducing Programmed Cell Death: Opening a New Window for Cancer Therapy DOI Creative Commons
Nilmadhab Roy, Priyankar Paira

ACS Omega, Год журнала: 2024, Номер 9(19), С. 20670 - 20701

Опубликована: Апрель 16, 2024

The cellular defense system against exogenous substances makes therapeutics inefficient as intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS) or nitrogen (RNS) other free radicals produced by the therapeutics. In cancer cell microenvironment, GSH level becomes exceptionally high to fight oxidative stress created production of ROS/RNS any radicals, which are byproducts redox reactions respiration processes. Thus, order maintain homeostasis for survival cells and their rapid proliferation, starts escalate. this circumstance, administration anticancer is vain, elevated reduces potential reduction they produce. Therefore, augment therapeutic agents condition, must be depleted hook crook. Hence, Review aims compile precisely role cells, importance its depletion therapy examples a few selected metal complexes able trigger death depleting level.

Язык: Английский

Процитировано

13