System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 29, 2022

The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis an iron-mediated form cell death caused by the accumulation lipid peroxides. intracellular imbalance between oxidant and antioxidant due abnormal expression multiple redox active enzymes will promote produce reactive oxygen species (ROS). So far, few pathways regulators have been discovered regulate ferroptosis. In particular, cystine/glutamate antiporter (System X c − ), glutathione peroxidase 4 (GPX4) (GSH) /GSH/GPX4 axis) plays key role in preventing peroxidation-mediated ferroptosis, because which could be inhibited blocking System axis. This review aims present current understanding mechanism based on axis treatment

Language: Английский

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Overcoming cancer chemotherapy resistance by the induction of ferroptosis

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 66, P. 100916 - 100916

Published: Dec. 29, 2022

Language: Английский

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Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Ferroptosis is a new form of regulated cell death, which mediated by intracellular iron. Although it reported that bavachin has antitumour effects on several tumour cells and prompts the reactive oxygen species (ROS) generation, unclear whether ferroptosis can be induced in osteosarcoma (OS) cells. In this study, we found inhibits viability MG63 HOS OS lines along with an increase ferrous iron level, ROS accumulation, malondialdehyde overexpression, glutathione depletion. Moreover, chelators (deferoxamine), antioxidants (Vit E), inhibitors (ferrostatin-1 liproxstatin-1) reverse bavachin-induced death. Bavachin also altered mitochondrial morphology cells, leading to smaller mitochondria, higher density membrane, reduced cristae. Further investigation showed upregulated expression transferrin receptor, divalent metal transporter-1, P53, downregulating ferritin light chain, heavy p-STAT3 (705), SLC7A11, peroxidase-4 More importantly, STAT3 SLC7A11 pretreatment pifithrin-α (P53 inhibitor) rescued bavachin. The results show induces via STAT3/P53/SLC7A11 axis

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

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: April 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

Language: Английский

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Implication of ferroptosis in aging

Cell Death Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: June 28, 2021

Abstract Life is indeed continuously going through the irreversible and inevitable process of aging. The rate aging depends on various factors varies individually. These include environmental stimuli including exposure to toxic chemicals, psychological stress whereas suffering with illnesses specially chronic diseases serve as endogenous triggers. basic underlying mechanism for all kinds stresses now known be manifested production excessive ROS, exhaustion ROS neutralizing antioxidant enzymes proteins leading imbalance in oxidation processes subsequent oxidative induced inflammation affecting cells, tissues, organs whole body. All these lead conventional cell death either necrosis, apoptosis, or autophagy. Currently, a newly identified iron dependent regulated called ferroptosis, special interest its implication pathogenesis such cardiovascular disease, neurological disorders, cancers, other age-related disorders (ARD). In occur neither by necrosis nor autophagy, rather dysregulated mediates lipid peroxidation accumulated lethal lipids. It not surprising assume role previous research have some solid cues subject. this review, we will highlight factual evidences support possible ferroptosis order declare need identify explore interventions prevent accelerated associated liabilities

Language: Английский

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The Role of SLC7A11 in Cancer: Friend or Foe?

Cancers, Journal Year: 2022, Volume and Issue: 14(13), P. 3059 - 3059

Published: June 22, 2022

SLC7A11 controls the uptake of extracellular cystine in exchange for glutamate at a ratio 1:1, and it is overexpressed variety tumours. Accumulating evidence has shown that expression fine-tuned multiple levels, plays diverse functional pharmacological roles tumours, such as cellular redox homeostasis, cell growth death, metabolism. Many reports have suggested inhibition activity favourable tumour therapy; thus, regarded potential therapeutic target. However, emerging also suggests on some occasions, beneficial to survival cancer cells, confers development drug resistance. In this review, we first briefly introduce biological properties SLC7A11, including its structure physiological functions, further summarise regulatory network regulators. Then, focusing role cancer, describe relationships with tumourigenesis, survival, proliferation, metastasis, resistance more detail. Finally, since been linked through approaches, propose contribution mechanism require elucidation. Thus, personalised strategies should be adapted when targeting SLC7A11.

Language: Английский

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Hedyotis diffusa injection induces ferroptosis via the Bax/Bcl2/VDAC2/3 axis in lung adenocarcinoma

Phytomedicine, Journal Year: 2022, Volume and Issue: 104, P. 154319 - 154319

Published: July 8, 2022

Lung cancer has the highest mortality rate among all types. In combination with multiple chemotherapeutic options, traditional Chinese medicine proven indispensable for comprehensive treatment of lung cancer. To investigate effects Hedyotis diffusa on adenocarcinoma cell lines and a BALB/c nude mouse xenograft model, determine whether HDI could induce ferroptosis in cells along underlying mechanism. The anti-tumor activity was determined vitro by counting kit-8, clonogenic, transwell assays. Subsequently, electron microscopy, lipid reactive oxygen species assay, ferrous ion staining, malondialdehyde assay were performed to effect cells. mechanism then further investigated using small molecule inhibitors, siRNA, plasmid overexpression vitro. Finally, assessed tumor-bearing mice, HE staining observe tissue damage after treatment. experiments showed that inhibit viability via mechanisms independent GPX4 PUFA-PLS pathways but closely associated VDAC2/3. regulated VDAC2/3 promoting Bax inhibiting Bcl2, thereby inducing Furthermore, vivo significantly inhibited growth subcutaneous tumors mice less organ toxicity, increased expression ferroptosis-related indicators 4HNE, TFR, HMOX1 tumor tissue. can reduce survival vitro, subcutaneously transplanted vivo, Bcl2 inhibition promote regulation

Language: Английский

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The epigenetic regulatory mechanisms of ferroptosis and its implications for biological processes and diseases

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 22, 2023

Abstract Ferroptosis is a form of regulated cell death triggered by the iron‐dependent peroxidation phospholipids. Interactions iron and lipid metabolism factors jointly promote ferroptosis. has been demonstrated to be involved in development various diseases, such as tumors degenerative diseases (e.g., aortic dissection), targeting ferroptosis expected an effective strategy for treatment these diseases. Recent studies have shown that regulation affected multiple mechanisms, including genetics, epigenetics, posttranscriptional modifications, protein posttranslational modifications. Epigenetic changes garnered considerable attention due their importance regulating biological processes potential druggability. There many on epigenetic ferroptosis, histone modifications acetylation methylation), DNA methylation, noncoding RNAs miRNAs, circRNAs, lncRNAs). In this review, we summarize recent advances research mechanisms with description RNA N 6 ‐methyladenosine (m A) methylation included, ferroptosis‐related which provides reference clinical application regulators related

Language: Английский

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FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma

BMC Cancer, Journal Year: 2023, Volume and Issue: 23(1)

Published: Feb. 22, 2023

This research aimed to investigate the roles of fanconi anemia complementation group D2 (FANCD2) on regulation ferroptosis in osteosarcoma progression.The function FANCD2 cell viability, invasion, migration, and tumor growth were explored. pathway-related genes determined by western blot. Ferroptosis-associated markers determined, including lipid peroxidation, labile iron pool (LIP), ferrous (Fe2+), ferroptosis-related genes.FANCD2 expression was increased cells. knockdown reduced migration regulated gene expression, distinctly levels LIP, Fe2+, these effects reversed a inhibitor Fer-1. In addition, JAK2 STAT3 silencing FANCD2, activator (colivelin) suppressor development.These findings suggested that could suppress growth, induced regulating JAK2/STAT3 axis. These may provide novel therapeutic ideas for clinical treatment osteosarcoma.

Language: Английский

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