Inhibition of keratinocyte ferroptosis suppresses psoriatic inflammation DOI Creative Commons
Yanhong Shou, Lu Yang, Yongsheng Yang

et al.

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(11)

Published: Oct. 27, 2021

Abstract Psoriasis is a common, chronic, and recurrent inflammatory disease. It characterized by hyperproliferation abnormal differentiation of keratinocytes. Keratinocyte death also involved in many pathophysiological conditions amplifies the cascade. As newly recognized form cell death, ferroptosis several diseases. In this study, we aimed to investigate previously unrecognized role for psoriasis. Ferroptosis mediated lipid peroxidation iron overload. Compared with normal lesions, mRNA expression acyl-CoA synthetase long-chain family member 4 ( ACSL4 ), prostaglandin-endoperoxide synthase 2 PTGS2 transferrin receptor TFRC ) were highly expressed psoriatic decreased levels glutathione peroxidase GPX4 ferritin light chain FTL heavy 1 FTH1 ). The protein consistent their levels. A similar tendency was observed erastin-treated human primary keratinocytes Imiquimod (IMQ)-induced model To correlation between inflammation peroxidation, analyzed single-cell RNA-sequencing data identified 15 types. There high activity oxidation Th22/Th17 response at level. Moreover, ferrostatin-1 (Fer-1), potent inhibitor suppressed ferroptosis-related changes alleviated psoriasiform dermatitis IMQ-induced models. Additionally, Fer-1 blocked responses vitro vivo, reducing production cytokines including TNF-α , IL-6 IL-1α IL-1β IL-17 IL-22 IL-23 . This study revealed an pattern which specific molecules enhance reactions

Language: Английский

Broadening horizons: the role of ferroptosis in cancer DOI
Xin Chen, Rui Kang, Guido Kroemer

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(5), P. 280 - 296

Published: Jan. 29, 2021

Language: Английский

Citations

2034
The Metabolic Underpinnings of Ferroptosis DOI Creative Commons
Jiashuo Zheng, Marcus Conrad

Cell Metabolism, Journal Year: 2020, Volume and Issue: 32(6), P. 920 - 937

Published: Nov. 20, 2020

Language: Английский

Citations

967
Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy DOI Creative Commons

Weitong Gao,

Yuqin Wang, Yang Zhou

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 20, 2022

Abstract In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not ICIs, partly caused absence of tumor-infiltrating lymphocytes (TILs), significantly limits application ICIs. Converting these “cold” into “hot” may ICIs is an unsolved question immunotherapy. Since it a general characteristic cancers resist apoptosis, induction non-apoptotic regulated cell death (RCD) emerging as new treatment strategy. Recently, several studies have revealed interaction between RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, necroptosis exhibit synergistic responses while possibly exerting inhibitory effects on responses. Thus, targeted therapies (inducers inhibitors) against combination with exert potent activity, resistant This review summarizes multilevel relationship immunity RCD, including necroptosis, potential targeting improve efficacy malignancy.

Language: Английский

Citations

612
Selenium Compounds as Novel Potential Anticancer Agents DOI Open Access
Dominika Radomska, Robert Czarnomysy,

Dominik Radomski

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(3), P. 1009 - 1009

Published: Jan. 20, 2021

The high number of new cancer incidences and the associated mortality continue to be alarming, leading search for therapies that would more effective less burdensome patients. As there is evidence Se compounds can have chemopreventive activity, studies begun establish whether these also affect already existing cancers. This review aims discuss different classes Se-containing compounds, both organic inorganic, natural synthetic, mechanisms molecular targets their anticancer activity. chemical discussed in this paper include inorganic (selenite, selenate) such as diselenides, selenides, selenoesters, methylseleninic acid, 1,2-benzisoselenazole-3[2H]-one selenophene-based derivatives, well selenoamino acids Selol.

Language: Английский

Citations

409
Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy DOI Creative Commons
Fan Yang, Yi Xiao, Jia-Han Ding

et al.

Cell Metabolism, Journal Year: 2022, Volume and Issue: 35(1), P. 84 - 100.e8

Published: Oct. 17, 2022

Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic strategies. Here, we integrated multiomics data our large cohort (n = 465) to develop atlas. We discovered that TNBCs had heterogeneous phenotypes ferroptosis-related metabolites and pathways. The luminal androgen receptor (LAR) subtype was characterized by upregulation oxidized phosphatidylethanolamines glutathione metabolism (especially GPX4), which allowed utilization GPX4 inhibitors induce ferroptosis. Furthermore, verified inhibition not only induced tumor but also enhanced antitumor immunity. combination anti-PD1 possessed greater efficacy than monotherapy. Clinically, higher expression correlated with lower cytolytic scores worse prognosis immunotherapy cohorts. Collectively, this study demonstrated landscape revealed an innovative strategy for refractory LAR tumors.

Language: Английский

Citations

326
The cell biology of ferroptosis DOI
Scott J. Dixon, James A. Olzmann

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 424 - 442

Published: Feb. 16, 2024

Language: Английский

Citations

305
Inhibition of ferroptosis by up-regulating Nrf2 delayed the progression of diabetic nephropathy DOI
Shuangwen Li,

Lisi Zheng,

Jun Zhang

et al.

Free Radical Biology and Medicine, Journal Year: 2020, Volume and Issue: 162, P. 435 - 449

Published: Nov. 2, 2020

Language: Английский

Citations

301
Contribution of ferroptosis and GPX4’s dual functions to osteoarthritis progression DOI
Miao Yu, Yiwei Chen, Feng Xue

et al.

EBioMedicine, Journal Year: 2022, Volume and Issue: 76, P. 103847 - 103847

Published: Feb. 1, 2022

Language: Английский

Citations

300
Tagitinin C induces ferroptosis through PERK-Nrf2-HO-1 signaling pathway in colorectal cancer cells DOI Creative Commons

Ruiran Wei,

Yueqin Zhao,

Juan Wang

et al.

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(11), P. 2703 - 2717

Published: Jan. 1, 2021

Rationale: Colorectal cancer (CRC) is a common malignant tumor of the digestive system. However, efficacy surgery and chemotherapy limited. Ferroptosis an iron- reactive oxygen species (ROS)-dependent form regulated cell death (RCD) plays vital role in suppression. inducing agents have been studied extensively as novel promising way to fight against therapy resistant cancers. The aim this study investigate mechanism action tagitinin C (TC), natural product, ferroptosis inducer Methods: response CRC cells was assessed by viability assay, clonogenic transwell migration cycle assay apoptosis assay. Molecular approaches including Western blot, RNA sequencing, quantitative real-time PCR immunofluorescence were employed well. Results: Tagitinin C, sesquiterpene lactone isolated from Tithonia diversifolia, inhibits growth colorectal HCT116 cells, induced oxidative cellular microenvironment resulting cells. C-induced accompanied with attenuation glutathione (GSH) levels increased lipid peroxidation. Mechanistically, endoplasmic reticulum (ER) stress stress, thus activating nuclear translocation factor erythroid 2-related 2 (Nrf2). As downstream gene (effector) Nrf2, heme oxygenase-1 (HO-1) expression significantly treatment C. Upregulated HO-1 led increase labile iron pool, which promoted peroxidation, meanwhile showed synergistic anti-tumor effect together erastin. Conclusion: In summary, we provided evidence that induces has through ER stress-mediated activation PERK-Nrf2-HO-1 signaling pathway. identified inducer, may be effective chemosensitizer can expand range chemotherapeutic agents.

Language: Английский

Citations

291
Ferroptosis in Liver Diseases: An Overview DOI Open Access
Martina Maria Capelletti, Hana Manceau, Hervé Puy

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(14), P. 4908 - 4908

Published: July 11, 2020

Ferroptosis is an iron-dependent form of cell death characterized by intracellular lipid peroxide accumulation and redox imbalance. shows specific biological morphological features when compared to the other patterns. The loss repair activity glutathione peroxidase 4 (GPX4), presence redox-active iron oxidation polyunsaturated fatty acid (PUFA)-containing phospholipids are considered as distinct fingerprints ferroptosis. Several pathways, including amino metabolism, ferritinophagy, adhesion, p53, Keap1/Nrf2 phospholipid biosynthesis, can modify susceptibility Through decades, various diseases, acute kidney injury; cancer; ischemia–reperfusion cardiovascular, neurodegenerative hepatic disorders, have been associated with In this review, we provide a comprehensive analysis main biochemical mechanisms ferroptosis overview chemicals used inducers inhibitors. Then, report contribution spectrum liver or chronic. Finally, discuss use therapeutic approach against hepatocellular carcinoma, most common primary cancer.

Language: Английский

Citations

276