Targeting Ferroptosis to Iron Out Cancer

Cancer Cell, Journal Year: 2019, Volume and Issue: 35(6), P. 830 - 849

Published: May 16, 2019

Language: Английский

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Oxidative Stress in Cancer

Cancer Cell, Journal Year: 2020, Volume and Issue: 38(2), P. 167 - 197

Published: July 9, 2020

Language: Английский

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Targeting ferroptosis as a vulnerability in cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(7), P. 381 - 396

Published: March 25, 2022

Language: Английский

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Mechanisms of ferroptosis

Cellular and Molecular Life Sciences, Journal Year: 2016, Volume and Issue: 73(11-12), P. 2195 - 2209

Published: April 5, 2016

Ferroptosis is a non-apoptotic form of cell death that can be triggered by small molecules or conditions inhibit glutathione biosynthesis the glutathione-dependent antioxidant enzyme peroxidase 4 (GPX4). This lethal process defined iron-dependent accumulation lipid reactive oxygen species and depletion plasma membrane polyunsaturated fatty acids. Cancer cells with high level RAS-RAF-MEK pathway activity p53 expression may sensitized to this process. Conversely, number molecule inhibitors ferroptosis have been identified, including ferrostatin-1 liproxstatin-1, which block pathological events in brain, kidney other tissues. Recent work has identified genes required for ferroptosis, those involved amino acid metabolism. Outstanding questions include relationship between forms death, whether activation inhibition exploited achieve desirable therapeutic ends.

Language: Английский

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The development of the concept of ferroptosis

Free Radical Biology and Medicine, Journal Year: 2018, Volume and Issue: 133, P. 130 - 143

Published: Sept. 27, 2018

Language: Английский

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Targeting mutant p53 for efficient cancer therapy

Nature reviews. Cancer, Journal Year: 2017, Volume and Issue: 18(2), P. 89 - 102

Published: Dec. 15, 2017

Language: Английский

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The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity

Cell Reports, Journal Year: 2017, Volume and Issue: 20(7), P. 1692 - 1704

Published: Aug. 1, 2017

Ferroptosis is a form of regulated cell death that may facilitate the selective elimination tumor cells. The suppressor p53 (TP53) has been demonstrated to promote ferroptosis via transcription-dependent mechanism. Here, we show TP53 limits erastin-induced by blocking dipeptidyl-peptidase-4 (DPP4) activity in transcription-independent manner. Loss prevents nuclear accumulation DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results ferroptosis. These findings reveal direct molecular link between control metabolism provide precision medicine strategy for treatment colorectal cancer induction

Language: Английский

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The emerging role of ferroptosis in inflammation

Biomedicine & Pharmacotherapy, Journal Year: 2020, Volume and Issue: 127, P. 110108 - 110108

Published: March 29, 2020

Ferroptosis is a newly discovered type of cell death triggered by intracellular phospholipid peroxidation that morphologically, biologically and genetically distinct from other types death. classified as regulated necrosis more immunogenic than apoptosis. To date, compelling evidence indicates ferroptosis plays an important role in inflammation, several antioxidants functioning inhibitors have been shown to exert anti-inflammatory effects experimental models certain diseases. Our review provides overview the link between inflammation; better understanding mechanisms underlying inflammation may hasten development promising therapeutic strategies involving address inflammation.

Language: Английский

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The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches

Annual Review of Biochemistry, Journal Year: 2016, Volume and Issue: 85(1), P. 375 - 404

Published: May 5, 2016

Inactivation of the transcription factor p53, through either direct mutation or aberrations in one its many regulatory pathways, is a hallmark virtually every tumor. In recent years, screening for p53 activators and better understanding molecular mechanisms oncogenic perturbations function have opened up host novel avenues therapeutic intervention cancer: from structure-guided design chemical chaperones to restore conformationally unstable cancer mutants, development potent antagonists negative regulators MDM2 MDMX other modulators pathway treatment cancers with wild-type p53. Some these compounds now moved proof-of-concept studies into clinical trials, prospects further, personalized anticancer medicines. We trace structural evolution pathway, germ-line surveillance simple multicellular organisms pluripotential role humans.

Language: Английский

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p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells

Cell Reports, Journal Year: 2018, Volume and Issue: 22(3), P. 569 - 575

Published: Jan. 1, 2018

How cancer cells respond to nutrient deprivation remains poorly understood. In certain cells, of cystine induces a non-apoptotic, iron-dependent form cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, high-resolution, time-lapse imaging, we find stabilization wild-type p53 delays onset in response deprivation. This delay requires transcriptional target CDKN1A (encoding p21) is associated with both slower depletion intracellular glutathione reduced accumulation toxic lipid-reactive oxygen species (ROS). Thus, p53-p21 axis help cope metabolic stress induced delaying non-apoptotic death.

Language: Английский

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