Biological Trace Element Research, Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 14, 2024
Language: Английский
Redox Biology, Journal Year: 2022, Volume and Issue: 54, P. 102351 - 102351
Published: May 28, 2022
The nonnegligible reason for the poor prognosis of hepatocellular carcinoma (HCC) is resistance to conventional chemotherapy. Immunogenic cell death (ICD) a rare immunostimulatory form that can reengage tumor-specific immune system. ICD improve clinical outcomes chemotherapeutics by promoting long-term cancer immunity. discovery potential inducers emerging as promising direction. In present study, micheliolide (MCL), natural guaianolide sesquiterpene lactone, was screened out virtual screening strategies, identified an inhibitor thioredoxin reductase (TrxR) and evaluated have high induce ICD. Here, we showed MCL induced ICD-associated DAMPs (damage-associated molecular patterns, such CRT exposure, ATP secretion HMGB1 release). significantly triggered regression established tumors in immunocompetent mouse vaccine model, (DCs maturation, stimulation CD4+, CD8+ T-cells responses) vivo. Mechanistically, found magnitude effects upon exposure HCC cells dependent on generation reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ERS). addition, suppression ROS normalized MCL-induced ERS, contrast, downregulation TrxR synergized with ERS driven MCL. We also systematically detected H2O2 using Hyper7 sensors exposed Notably, inhibited development organoids. Collectively, our results reveal association between inhibitors ICD, presenting valuable insights into MCL-activated cells.
Language: Английский
Citations
86
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116112 - 116112
Published: Jan. 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.
Language: Английский
Citations
41
Cancer Communications, Journal Year: 2024, Volume and Issue: 44(2), P. 185 - 204
Published: Jan. 13, 2024
Abstract Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, intermediates for biomolecule synthesis, modulates enzyme activity to sustain normal cellular functions. foundation of life processes plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis recently discovered form iron‐dependent The inhibition ferroptosis crucial tumorigenesis tumor progression. However, metabolism, particularly glucose amino acid cancer not well understood. Here, we reviewed glucose, lipid, acid, iron selenium involvement elucidate impact different metabolic pathways on this process. Additionally, provided detailed overview agents used induce ferroptosis. We explained that maintaining intracellular redox homeostasis disrupting these renders them more susceptible iron‐induced death, resulting enhanced killing. combination inducers inhibitors may be novel approach future therapy an important strategy advance development treatments.
Language: Английский
Citations
23
Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103032 - 103032
Published: Jan. 21, 2024
Thioredoxin (Trx) is a compact redox-regulatory protein that modulates cellular redox state by reducing oxidized proteins. Trx exhibits dual functionality as an antioxidant and cofactor for diverse enzymes transcription factors, thereby exerting influence over their activity function. has emerged pivotal biomarker various diseases, particularly those associated with oxidative stress, inflammation, aging. Recent clinical investigations have underscored the significance of in disease diagnosis, treatment, mechanistic elucidation. Despite its paramount importance, intricate interplay between senescence-a condition characterized irreversible growth arrest induced multiple aging stimuli-remains inadequately understood. In this review, our objective to present comprehensive up-to-date overview structure function Trx, involvement signaling pathways senescence, association age-related well potential therapeutic target. Our review aims elucidate novel extensive role senescence while highlighting implications diseases.
Language: Английский
Citations
21
Antioxidants and Redox Signaling, Journal Year: 2022, Volume and Issue: unknown
Published: June 10, 2022
Significance: Thioredoxin (Trx) is a powerful antioxidant that reduces protein disulfides to maintain redox stability in cells and involved regulating multiple redox-dependent signaling pathways. Recent Advance: The current accumulation of findings suggests Trx participates pathways interact with various proteins manipulate their dynamic regulation structure function. These network are critical for cancer pathogenesis therapy. Promising clinical advances have been presented by most anticancer agents targeting such Critical Issues: We herein link the regulated system potential therapeutic opportunities, focusing on coordination strengths apoptosis, ferroptosis, immunomodulation, drug resistance. also provide mechanistic exploitation small molecules Future Directions: As research data accumulate, future complex networks Trx-related will gain detail. In-depth exploration establishment these pathways, including upstream downstream regulatory proteins, be advancing novel therapeutics. Antioxid. Redox Signal. 38, 403-424.
Language: Английский
Citations
37
Biomolecules, Journal Year: 2022, Volume and Issue: 12(11), P. 1581 - 1581
Published: Oct. 28, 2022
A potential target of precision nutrition in cancer therapeutics is the micronutrient selenium (Se). Se metabolized and incorporated as amino acid selenocysteine (Sec) into 25 human selenoproteins, including glutathione peroxidases (GPXs) thioredoxin reductases (TXNRDs), among others. Both processes Sec metabolism for production selenoproteins action are utilized by cells from solid tumors a protective mechanism against oxidative damage to resist ferroptosis, an iron-dependent cell death mechanism. Protection ferroptosis requires sustained selenoprotein GPX4, which involves increasing uptake Se, potentially activating metabolic pathways such trans-selenation pathway TXNRD1-dependent decomposition inorganic selenocompounds sustain GPX4 synthesis. Additionally, endoplasmic reticulum-resident also affect apoptotic responses presence selenocompounds. Selenoproteins may help adapting increased challenges modified nutrient that result Warburg switch. Finally, rewire hierarchy use Se-related machinery prioritize essential adaptations damage. In this review, we discuss both evidence gaps knowledge on how Sec, promote their survival particularly via resistance ferroptosis.
Language: Английский
Citations
33
Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(5), P. 988 - 997
Published: Sept. 22, 2023
Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation, differing from apoptosis, necroptosis, autophagy in several aspects. regarded as critical mechanism series pathophysiological reactions after stroke because overload caused hemoglobin degradation metabolism imbalance. In this review, we discuss ferroptosis-related metabolisms, important molecules directly or indirectly targeting transcriptional regulation ferroptosis, revealing the role ferroptosis progression stroke. We present updated progress intervention therapeutic strategies for vivo vitro summarize effects inhibitors on Our review facilitates further understanding pathogenesis stroke, proposes new targets treatment suggests that more efforts should be made to investigate
Language: Английский
Citations
20
Cancer Drug Resistance, Journal Year: 2023, Volume and Issue: 6(4), P. 709 - 27
Published: Oct. 16, 2023
The induction of cell death is recognized as a potent strategy for cancer treatment. Apoptosis an extensively studied form death, and multiple anticancer drugs exert their therapeutic effects by inducing it. Nonetheless, apoptosis evasion hallmark cancer, rendering cells resistant to chemotherapy drugs. Consequently, there growing interest in exploring novel non-apoptotic forms such ferroptosis, necroptosis, pyroptosis, paraptosis. Natural compounds with properties have garnered significant attention due advantages, including reduced risk drug resistance. Over the past two decades, numerous natural been discovered anti-resistance triggering these four mechanisms. This review primarily focuses on mechanisms recent advancements overcoming resistance Meanwhile, it highlights role effectively addressing through death.
Language: Английский
Citations
18
Antioxidants, Journal Year: 2024, Volume and Issue: 13(9), P. 1078 - 1078
Published: Sept. 4, 2024
Cells constantly face the challenge of managing oxidants. In aerobic organisms, oxygen (O
Language: Английский
Citations
8
Antioxidants and Redox Signaling, Journal Year: 2023, Volume and Issue: 40(1-3), P. 40 - 85
Published: May 3, 2023
The multifactorial nature of the mechanisms implicated in cancer development still represents a major issue for success established antitumor therapies. discovery ferroptosis, novel form programmed cell death distinct from apoptosis, along with identification molecular pathways activated during its execution, has led to uncovering molecules characterized by ferroptosis-inducing properties.
Language: Английский
Citations
14