The diversified role of mitochondria in ferroptosis in cancer

Cell Death and Disease, Год журнала: 2023, Номер 14(8)

Опубликована: Авг. 14, 2023

Abstract Ferroptosis is a form of regulated cell death induced by iron-dependent lipid peroxidation, and it has been studied extensively since its discovery in 2012. Induced iron overload ROS accumulation, ferroptosis modulated various cellular metabolic signaling pathways. The GSH-GPX4 pathway, the FSP1-CoQ10 GCH1-BH4 DHODH-CoQH2 system sex hormones suppress ferroptosis. Mitochondrial metabolism regulates mitochondria also undergo morphological change during ferroptosis, these changes include increased membrane density reduced mitochondrial cristae. Moreover, energy oxidative phosphorylation ATP production rates lead to decrease glycolysis rate. In addition, excessive stress induces irreversible damage mitochondria, diminishing organelle integrity. production, potential, fusion fission, mitophagy function Notably, some inhibitors target mitochondria. major mechanism for associated with progression cancer. Metastasis-prone or metastatic cancer cells are more susceptible Inducing tumor shows very promising potential treating drug-resistant cancers. this review, we present brief retrospect characteristics then discuss regulation highlight unique role played cells. Furthermore, explain how functions as double-edged sword well novel therapies aimed at selectively manipulating eradication.

Язык: Английский

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SLC7A11 as a Gateway of Metabolic Perturbation and Ferroptosis Vulnerability in Cancer

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

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The Mechanisms of Ferroptosis Under Hypoxia

Cellular and Molecular Neurobiology, Год журнала: 2023, Номер 43(7), С. 3329 - 3341

Опубликована: Июль 17, 2023

Abstract Ferroptosis is a new form of programmed cell death, which characterized by the iron-dependent accumulation lipid peroxidation and increase ROS, resulting in oxidative stress death. Iron, lipid, multiple signaling pathways precisely control occurrence implementation ferroptosis. The mainly include Nrf2/HO-1 pathway, p62/Keap1/Nrf2 pathway. Activating pathway inhibits promotes Furthermore, some factors also participate ferroptosis under hypoxia, such as HIF-1, NCOA4, DMT1. Meanwhile, related with hypoxia-related diseases, MIRI, cancers, AKI. Accordingly, appears to be therapeutic target for diseases.

Язык: Английский

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GPX4, ferroptosis, and diseases

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

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Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Апрель 1, 2023

Lung cancer is a common malignant tumor that occurs in the human body and poses serious threat to health quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, radiotherapy. However, due strong metastatic characteristics lung emergence related drug resistance radiation resistance, overall survival rate patients not ideal. There an urgent need develop new strategies or effective drugs treat cancer. Ferroptosis, novel type programmed cell death, different from traditional death pathways such as apoptosis, necrosis, pyroptosis so on. It caused by increase iron-dependent reactive oxygen species intracellular iron overload, which leads accumulation lipid peroxides, thus inducing membrane oxidative damage, affecting normal life process cells, finally promoting ferroptosis. regulation ferroptosis closely physiological it involves metabolism, balance between oxygen-free radical reaction peroxidation. A large number studies have confirmed result combined action cellular oxidation/antioxidant system damage/repair, has great potential application therapy. Therefore, this review aims explore therapeutic targets for clarifying regulatory pathway Based on study ferroptosis, mechanism was understood chemical natural compounds targeting were summarized, with aim providing ideas In addition, also provides basis discovery clinical effectively

Язык: Английский

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Research on ferroptosis as a therapeutic target for the treatment of neurodegenerative diseases

Ageing Research Reviews, Год журнала: 2023, Номер 91, С. 102035 - 102035

Опубликована: Авг. 23, 2023

Ferroptosis is an iron- and lipid peroxidation (LPO)-mediated programmed cell death type. Recently, mounting evidence has indicated the involvement of ferroptosis in neurodegenerative diseases, especially Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS), Huntington's (HD), so on. Treating presents opportunities as well challenges for diseases. This review provides a comprehensive overview underlying mechanisms that contribute to occurrence ferroptosis, their implications pathogenesis advancement major disorders. Meanwhile, we summarize interaction between other types diseases contribution corresponding drug development. In addition, specifically recent advances developing therapeutic means targeting these which may guide future approaches effective management devastating medical conditions.

Язык: Английский

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The mechanisms of ferroptosis and its role in atherosclerosis

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116112 - 116112

Опубликована: Янв. 2, 2024

Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation lethal lipid reactive oxygen species (ROS) and peroxidation membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). unique among other death modalities in many aspects. It initiated excessive oxidative damage due to iron overload compromised antioxidant defense systems, including system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway GPX4-independent pathways. In past ten years, ferroptosis was reported play critical role pathogenesis various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, myocardial ischemia-reperfusion injury. Studies have dysfunctional metabolism abnormal expression profiles ferroptosis-related factors, iron, GSH, GPX4, ferroportin (FPN), SLC7A11 (xCT), as indicators for atherogenesis. Moreover, plaque cells, i.e., vascular endothelial (VEC), macrophage, smooth muscle (VSMC), positively correlate with atherosclerotic development. Many macromolecules, drugs, Chinese herbs, food extracts can inhibit atherogenic process suppressing cells. contrast, some inducers significant pro-atherogenic effects. However, mechanisms through which affects progression AS still need be well-known. This review summarizes molecular their emerging AS, aimed at providing novel, promising druggable targets anti-AS therapy.

Язык: Английский

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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

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

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Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer

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

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Interplay of Ferroptosis and Cuproptosis in Cancer: Dissecting Metal-Driven Mechanisms for Therapeutic Potentials

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

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