Butyrate dictates ferroptosis sensitivity through FFAR2-mTOR signaling DOI Creative Commons

GuoYan Wang,

Senlin Qin,

Lei Chen

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(4)

Published: April 25, 2023

Evidence shows that short-chain fatty acids (SCFAs) play an important role in health maintenance and disease development. In particular, butyrate is known to induce apoptosis autophagy. However, it remains largely unclear whether can regulate cell ferroptosis, the mechanism by which has not been studied. this study, we found RAS-selective lethal compound 3 (RSL3)- erastin-induced ferroptosis were enhanced sodium (NaB). With regard underlying mechanism, our results showed NaB promoted inducing lipid ROS production via downregulating expression of solute carrier family 7 member 11 (SLC7A11) glutathione peroxidase 4 (GPX4). Moreover, FFAR2-AKT-NRF2 axis FFAR2-mTORC1 accounts for NaB-mediated downregulation SLC7A11 GPX4, respectively, a cAMP-PKA-dependent manner. Functionally, inhibit tumor growth inhibitory effect could be eliminated administrating MHY1485 (mTORC1 activator) Ferr-1 (ferroptosis inhibitor). Altogether, vivo suggest treatment correlated mTOR-dependent consequent through xenografts colitis-associated colorectal tumorigenesis, implicating potential clinical applications future cancer treatments. Based on all these findings, have proposed regulatory inhibits mTOR pathway control tumorigenesis.

Language: Английский

The Role of Cystine/Glutamate Antiporter SLC7A11/xCT in the Pathophysiology of Cancer DOI Creative Commons
Nidhi Jyotsana,

Kenny T. L. Ta,

Kathleen E. DelGiorno

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Feb. 23, 2022

SLC7A11/xCT is an antiporter that mediates the uptake of extracellular cystine in exchange for glutamate. Cystine reduced to cysteine, which a rate-limiting precursor glutathione synthesis; process protects cells from oxidative stress and is, therefore, critical cell growth, proliferation, metabolism. SLC7A11 expressed different tissues plays diverse functional roles pathophysiology various diseases, including cancer, by regulating processes redox homeostasis, metabolic flexibility/nutrient dependency, immune system function, ferroptosis. expression associated with poor prognosis drug resistance cancer and, represents important therapeutic target. In this review, we discuss molecular functions normal

Language: Английский

Citations

145
Targeting ferroptosis in acute kidney injury DOI Creative Commons
Lihua Ni, Yuan Cheng, Xiaoyan Wu

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(2)

Published: Feb. 24, 2022

Acute kidney injury (AKI) is a major public health problem with high incidence and mortality. As form of programmed cell death (PCD), ferroptosis could be considered as process iron accumulation enhanced lipid peroxidation. Recently, the fundamental roles in AKI have attracted much attention. The network mechanism its to chronic disease (CKD) transition complicated multifactorial. Strategies targeting show great potential. Here, we review research progress on participation AKI. We hope that this work will provide clues for further studies

Language: Английский

Citations

127
Ferroptosis as a potential target for cancer therapy DOI Creative Commons
Zhen Chen, Weilong Wang, Siti Razila Abdul Razak

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 24, 2023

Abstract Ferroptosis is a recently discovered essential type of cell death that mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests ferroptosis double-edged sword in human cancer. However, the precise underlying molecular mechanisms their differential roles tumorigenesis are unclear. Therefore, this review, we summarize briefly present key pathways ferroptosis, paying special attention to regulation as well its dual role an oncogenic tumor suppressor event various cancers. Moreover, multiple pharmacological activators summarized, prospect targeting cancer therapy further elucidated.

Language: Английский

Citations

110
SLC7A11 as a Gateway of Metabolic Perturbation and Ferroptosis Vulnerability in Cancer DOI Creative Commons
Jaewang Lee, Jong‐Lyel Roh

Antioxidants, Journal Year: 2022, Volume and Issue: 11(12), P. 2444 - 2444

Published: Dec. 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.

Language: Английский

Citations

90
Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis DOI Creative Commons
Yan Li, Wenjuan Yang, Yuanyuan Zheng

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Jan. 6, 2023

Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal drug by targeting ferroptosis. The present study aimed explore the association fatty acid synthase (FASN) sorafenib via regulation ferroptosis provide novel strategy overcome HCC patients.Intracellular levels lipid peroxides, glutathione, malondialdehyde, Fe2+ were measured as indicators status. Biological information analyses, immunofluorescence assays, western blot co-immunoprecipitation analyses conducted elucidate functions FASN in HCC. Both vitro vivo examine antitumor effects combination orlistat CalcuSyn software was used calculate index.Solute carrier family 7 member 11 (SLC7A11) found play an important role mediating resistance. up-regulation antagonize SLC7A11-mediated thereby promoted Mechanistically, enhanced sorafenib-induced binding hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination proteasomal degradation HIF1α, subsequently enhancing transcription SLC7A11. Orlistat, inhibitor FASN, had significant synergistic reversed both vivo.Targeting FASN/HIF1α/SLC7A11 pathway resensitized cells sorafenib. superior sorafenib-resistant cells.

Language: Английский

Citations

89
Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma DOI Creative Commons

Lingbo An,

Mingyang Li,

Qingge Jia

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 19, 2023

Abstract Esophageal squamous cell carcinoma (ESCC) is the sixth most common cause of cancer-related mortality worldwide, with more than half them occurred in China. Radiotherapy (RT) has been widely used for treating ESCC. However, radiation-induced DNA damage response (DDR) can promote release cytokines and chemokines, triggers inflammatory reactions changes tumor microenvironment (TME), thereby inhibiting immune function causing invasion metastasis Radioresistance major disease progression cancer, it associated heterogeneity. Therefore, a better understanding radioresistance mechanisms may generate reversal strategies to improve cure rates survival periods ESCC patients. We mainly summarized possible order reveal new targets therapy. Then we compared current reverse radioresistance.

Language: Английский

Citations

69
miRNAs role in bladder cancer pathogenesis and targeted therapy: Signaling pathways interplay – A review DOI
Hesham A. El-Mahdy, Elsayed G.E. Elsakka, Ahmed A. El-Husseiny

et al.

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 242, P. 154316 - 154316

Published: Jan. 20, 2023

Language: Английский

Citations

60
Metabolic heterogeneity in cancer DOI
Margherita Demicco, Xiao‐Zheng Liu, Katharina Leithner

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(1), P. 18 - 38

Published: Jan. 24, 2024

Language: Английский

Citations

59
Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy DOI Creative Commons
Nan Xing,

Qinyun Du,

Sa Guo

et al.

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

Citations

50
Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance DOI Creative Commons
Xudong Zhu, Shenglong Li

Advanced Science, Journal Year: 2023, Volume and Issue: 10(26)

Published: July 12, 2023

In recent years, the incidence of gastrointestinal cancers is increasing, particularly in younger population. Effective treatment crucial for improving patients' survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role growth and development organisms. It also critical maintaining tissue organ homeostasis takes part multiple pathological processes. addition to apoptosis, there are other types programmed such as ferroptosis, necroptosis, pyroptosis, which can induce severe inflammatory responses. Notably, besides pyroptosis contribute occurrence cancers. This review aims provide comprehensive summary on biological roles molecular mechanisms well their regulators hope open up new paths tumor targeted therapy near future.

Language: Английский

Citations

44