Radiation-Induced Lipid Peroxidation Triggers Ferroptosis and Synergizes with Ferroptosis Inducers

Ye, Ling F.; Chaudhary, Kunal; Zandkarimi, Fereshteh; Harken, Andrew; Kinslow, Connor J.; Upadhyayula, Pavan S.; Dovas, Athanassios; Higgins, Dominique; Tan, Hui; Zhang, Yan; Buonanno, Manuela; Wang, Tony J. C.; Hei, Tom K.; Bruce, Jeffrey N.; Canoll, Peter; Cheng, Simon K.; Stockwell, Brent R.

doi:10.1021/acschembio.9b00939

Cited by 350 publications

(250 citation statements)

References 46 publications

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“…The expression level of SLC7A11 is higher in either glioblastoma (GBM) patient biopsies or glioma cell lines than in normal brain tissues (44); thus, inhibiting system X − c or GPX4 by ferroptosis inducers enhances the therapeutic effect of radiation in breast cancer, sarcoma, and glioblastoma (40,41,(43)(44)(45). Khorsandi et al showed that the use of gallic acid (GA, a natural polyhydroxy phenolic compound) after pre-irradiation can significantly reduce the survival rate of breast cancer and melanoma cells mainly through inhibition of GPX4 activity without affecting normal cells (42).…”

Section: Ferroptosis In Cancer Radiotherapymentioning

confidence: 99%

Ferroptosis in Cancer Treatment: Another Way to Rome

Luo

et al. 2020

Front. Oncol.

124

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Ferroptosis is a newly described type of programmed cell death and intensively related to both maintaining homeostasis and the development of diseases, especially cancers. Inducing ferroptosis leads to mitochondrial dysfunction and toxic lipid peroxidation in cells, which plays a pivotal role in suppressing cancer growth and progression. Here, we reviewed the existing studies about the molecular mechanisms of ferroptosis involved in different antitumor treatments, such as chemotherapy, targeted therapy, radiotherapy, and immunotherapy. We focused in particular on the distinct combinatorial therapeutic effects such as the synergistic sensitization effect and the drug-resistance reversal achieved when using ferroptosis inducers with conventional cancer therapy. Finally, we discussed the challenges and opportunities in clinical applications of ferroptosis. The application of nanotechnolgy and other novel technologies may provide a new direction in ferroptosis-driven cancer therapies.

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Section: Ferroptosis In Cancer Radiotherapymentioning

confidence: 99%

Ferroptosis in Cancer Treatment: Another Way to Rome

Luo

et al. 2020

Front. Oncol.

124

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“…GBM is an ideal setting for testing this approach because it exhibits profound inter-and intratumoral heterogeneity and is the most common and deadly primary brain malignancy in adults. Surgical resection is part of the standard-of-care, and robust protocols for acute slice culture of human GBM have been established previously [4][5][6] . Furthermore, GBM has been extensively characterized by scRNA-seq providing a detailed baseline for both the transformed populations that co-occur in individual patients and the microenvironment [7][8][9][10][11] .…”

mentioning

confidence: 99%

Deconvolution of Cell Type-Specific Drug Responses in Human Tumor Tissue with Single-Cell RNA-seq

Zhao

Dovas

Spinazzi

et al. 2020

Preprint

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Precision oncology requires the timely selection of effective drugs for individual patients. An ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. Here we combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses. We applied this approach to glioblastoma (GBM) and demonstrated that acute slice cultures from individual patients recapitulate the cellular and molecular features of the originating tumor tissue. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients, including unexpected effects on the immune microenvironment. We anticipate that this approach will facilitate rapid, personalized drug screening to identify effective therapies for solid tumors.Inter-and intra-tumoral heterogeneity present major challenges for cancer therapy. Precision medicine, or targeted therapy, entails the use of agents that preferentially target tumor cells based on unique molecular features. The success of this approach relies on extensive characterization of tumor heterogeneity and microenvironment. While scRNA-seq can determine the cellular composition of complex tumors and even reveal cell type-specific drug sensitivities, these measurements are ultimately limited by models of

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“…This study exhibits a unique mechanism of ferroptosis protection independent of the GPX4/GSH system. In addition, mitochondrial DNA stress triggers autophagydependent ferroptosis death , and radiationinduced lipid peroxidation also triggers ferroptosis (Ye et al, 2020). These phenomena might be closely related to DNA damage, one of the causes of ferroptosis induced due to lipid peroxidation.…”

Section: Zheng Et Al 2020mentioning

confidence: 99%

Iron Metabolism and Ferroptosis in Epilepsy

Chen

Zhang

et al. 2020

Front. Neurosci.

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Epilepsy is a disease characterized by recurrent, episodic, and transient central nervous system (CNS) dysfunction resulting from an excessive synchronous discharge of brain neurons. It is characterized by diverse etiology, complex pathogenesis, and difficult treatment. In addition, most epileptic patients exhibit social cognitive impairment and psychological impairment. Iron is an essential trace element for human growth and development and is also involved in a variety of redox reactions in organisms. However, abnormal iron metabolism is associated with several neurological disorders, including hemorrhagic post-stroke epilepsy and post-traumatic epilepsy (PTE). Moreover, ferroptosis is also considered a new form of regulation of cell death, which is attributed to severe lipid peroxidation caused by the production of reactive oxygen species (ROS) and iron overload found in various neurological diseases, including epilepsy. Therefore, this review summarizes the study on iron metabolism and ferroptosis in epilepsy, in order to elucidate the correlation between iron and epilepsy. It also provides a novel method for the treatment, prevention, and research of epilepsy, to control epileptic seizures and reduce nerve injury after the epileptic seizure.

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Radiation-Induced Lipid Peroxidation Triggers Ferroptosis and Synergizes with Ferroptosis Inducers

Cited by 350 publications

References 46 publications

Ferroptosis in Cancer Treatment: Another Way to Rome

Ferroptosis in Cancer Treatment: Another Way to Rome

Deconvolution of Cell Type-Specific Drug Responses in Human Tumor Tissue with Single-Cell RNA-seq

Iron Metabolism and Ferroptosis in Epilepsy

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