Unlocking the Potential of Disulfidptosis: Nanotechnology‐Driven Strategies for Advanced Cancer Therapy DOI
Wenyao Zhen, Tianzhi Zhao, Xiaoyuan Chen

и другие.

Small, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Abstract Tumor tissues exhibit elevated oxidative stress, with the cystine‐glutamate transporter x CT solute carrier family 7 member 11 ( CT/SLC7A11) protecting cancer cells from damage by facilitating cystine uptake for glutathione synthesis. Disulfidptosis, a newly identified form of programmed cell death (PCD), occurs in high CT/SLC7A11 expression under glucose‐deprived conditions. Distinct other PCD pathways, disulfidptosis is characterized aberrant disulfide bond formation and cellular dysfunction, ultimately resulting death. This novel mechanism offers remarkable therapeutic potential targeting inherent stress vulnerabilities rapidly growing cells. Advances nanotechnology enable development nanomaterials capable inducing reactive oxygen species (ROS) generation, disrupting bonds. In addition, they are to deliver agents directly tumors, thereby improving precision minimizing off‐target effects. Moreover, combining ROS‐induced immunogenic can remodel tumor microenvironment enhance anti‐tumor immunity. review explores mechanisms underlying disulfidptosis, its treatment, synergistic role amplifying Selective induction using represents promising strategy achieving more effective, selective, less toxic therapies.

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

91
Targeting GPX4 in human cancer: Implications of ferroptosis induction for tackling cancer resilience DOI
Jaewang Lee, Jong‐Lyel Roh

Cancer Letters, Год журнала: 2023, Номер 559, С. 216119 - 216119

Опубликована: Март 7, 2023

Язык: Английский

Процитировано

61
miR-509–5p promotes colorectal cancer cell ferroptosis by targeting SLC7A11 DOI
Mahmoud A. Elrebehy, Tamer M. Abdelghany,

Mostafa M. Elshafey

и другие.

Pathology - Research and Practice, Год журнала: 2023, Номер 247, С. 154557 - 154557

Опубликована: Май 20, 2023

Язык: Английский

Процитировано

48
ACSL1-induced ferroptosis and platinum resistance in ovarian cancer by increasing FSP1 N-myristylation and stability DOI Creative Commons
Qingyu Zhang, Ning Li, Limei Deng

и другие.

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

Опубликована: Март 8, 2023

Reprogramming of lipid metabolism, which modulates energy utilization and cell signaling, maintains survival promotes cancer metastasis in cells. Ferroptosis is a type necrosis caused by an overload oxidation, has been demonstrated to be involved metastasis. However, the mechanism fatty acid metabolism regulates anti-ferroptosis signaling pathways not fully understood. The formation ovarian spheroids helps counteract hostile microenvironment peritoneal cavity with low oxygen, shortage nutrients, subjected platinum therapy. Previously, we that Acyl-CoA synthetase long-chain family member 1 (ACSL1) metastases cancer, but still well elucidated. In this study, demonstrate under exposure chemotherapy increased levels proteins as ACSL1. Inhibition ferroptosis can enhance spheroid vice versa. Genetic manipulation ACSL1 expression showed reduced level oxidation resistance ferroptosis. Mechanistically, N-myristoylation suppressor (FSP1), resulting inhibition its degradation translocation membrane. increase myristoylated FSP1 functionally counteracted oxidative stress-induced Clinical data also suggested protein was positively correlated negatively markers 4-HNE PTGS2. conclusion, study enhances antioxidant capacity increases modulating myristoylation FSP1.

Язык: Английский

Процитировано

45
Cystine deprivation triggers CD36-mediated ferroptosis and dysfunction of tumor infiltrating CD8+ T cells DOI Creative Commons

Chenfeng Han,

Minmin Ge,

Pengfei Xing

и другие.

Cell Death and Disease, Год журнала: 2024, Номер 15(2)

Опубликована: Фев. 15, 2024

Abstract Cancer cells develop multiple strategies to evade T cell-mediated killing. On one hand, cancer may preferentially rely on certain amino acids for rapid growth and metastasis. the other sufficient nutrient availability uptake are necessary mounting an effective cell anti-tumor response in tumor microenvironment (TME). Here we demonstrate that outcompete cystine due high Slc7a11 expression. This competition induces T-cell exhaustion ferroptosis, characterized by diminished memory formation cytokine secretion, increased PD-1 TIM-3 expression, as well intracellular oxidative stress lipid-peroxide accumulation. Importantly, either deletion or intratumoral supplementation improves immunity. Mechanistically, deprivation disrupts glutathione synthesis, but promotes CD36 mediated lipid dysregulated cystine/glutamate exchange. Moreover, enforced expression of glutamate-cysteine ligase catalytic subunit (Gclc) synthesis prevents upregulation, thus boosting Our findings reveal metabolic checkpoint orchestrates survival differentiation, highlight Gclc a potential therapeutic target enhancing function.

Язык: Английский

Процитировано

28
Recent Progress in Anti‐Tumor Nanodrugs Based on Tumor Microenvironment Redox Regulation DOI

Lan Yao,

Zhu Xiang,

Yunyi Shan

и другие.

Small, Год журнала: 2024, Номер 20(25)

Опубликована: Янв. 25, 2024

Abstract The growth state of tumor cells is strictly affected by the specific abnormal redox status microenvironment (TME). Moreover, reactions at biological level are also central and fundamental to essential energy metabolism in tumors. Accordingly, anti‐tumor nanodrugs targeting disruption this homeostasis have become one hot spots field research due effectiveness TME modulation efficiency mediated interference. This review discusses latest results therapy, which regulate levels oxidants or reductants through a variety therapeutic strategies, ultimately breaking original “stable” promoting cell death. With gradual deepening study on vigorous development nanomaterials, it expected that more nano drugs based regulation will be designed even applied clinically.

Язык: Английский

Процитировано

20
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

28
Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions DOI Creative Commons
Jinyu Chen,

Boyuan Ma,

Yubiao Yang

и другие.

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Апрель 29, 2024

Abstract Cell death is an important part of the life cycle, serving as a foundation for both orderly development and maintenance physiological equilibrium within organisms. This process fundamental, it eliminates senescent, impaired, or aberrant cells while also promoting tissue regeneration immunological responses. A novel paradigm programmed cell death, known disulfidptosis, has recently emerged in scientific circle. Disulfidptosis defined accumulation cystine by cancer with high expression solute carrier family 7 member 11 (SLC7A11) during glucose starvation. causes extensive disulfide linkages between F-actins, resulting their contraction subsequent detachment from cellular membrane, triggering death. The RAC1-WRC axis involved this phenomenon. sparked growing interest due to its potential applications variety pathologies, particularly oncology, neurodegenerative disorders, metabolic anomalies. Nonetheless, complexities regulatory pathways remain elusive, precise molecular targets have yet be definitively identified. manuscript aims meticulously dissect historical evolution, underpinnings, frameworks, implications disulfidptosis various disease contexts, illuminating promise groundbreaking therapeutic pathway target.

Язык: Английский

Процитировано

12
Iron accumulation and lipid peroxidation: implication of ferroptosis in hepatocellular carcinoma DOI Creative Commons
Xiaodong Li,

Fanguang Meng,

Hankang Wang

и другие.

Frontiers in Endocrinology, Год журнала: 2024, Номер 14

Опубликована: Янв. 4, 2024

Ferroptosis is a type of controlled cell death caused by lipid peroxidation, which results in the rupture membrane. ferroptosis has been repeatedly demonstrated over past ten years to be significant factor number diseases. The liver iron storage organ, thus will have great potential treatment particularly prevalent HCC. In opening section this article, we give general summary pertinent molecular mechanisms, signaling pathways, and associated characteristics ferroptosis. primary regulating mechanisms during are then briefly discussed, conclude summarizing development novel therapeutic strategies used treat HCC recent years. crucial strategy for offers new perspectives on cancer.

Язык: Английский

Процитировано

10
ROS‐Responsive Injectable Hydrogel Loaded with SLC7A11‐modRNA Inhibits Ferroptosis and Mitigates Intervertebral Disc Degeneration in Rats DOI

Tian Gao,

Guangyu Xu, Tiancong Ma

и другие.

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(27)

Опубликована: Май 1, 2024

Abstract Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, with oxidative stress being a recognized factor that causes its development. Presently, pain imposes significant global economic burden. However, effectiveness treatments for IVDD remains extremely limited. Therefore, this study aims to explore innovative and effective by focusing on as starting point. In study, an injectable reactive oxygen species‐responsive hydrogel (PVA‐tsPBA@SLC7A11 modRNA) developed, designed achieve rapid loading selective release chemically synthesized modified mRNA (modRNA). SLC7A11 modRNA specifically used upregulate expression ferroptosis marker SLC7A11. The local injection PVA‐tsPBA@SLC7A11 into degenerated intervertebral (IVD) results in cleavage PVA‐tsPBA, leading enclosed modRNA. extent directly proportional severity IVDD, ultimately ameliorating inhibiting nucleus pulposus cells (NPCs). This proposes system PVA‐tsPBA hydrogel‐encapsulated modRNA, representing potential novel treatment strategy patients early‐stage IVDD.

Язык: Английский

Процитировано

10