Influx rate of 18F-fluoroaminosuberic acid reflects cystine/glutamate antiporter expression in tumour xenografts

Pitman, Kathinka E.; Alluri, Santosh Reddy; Kristian, Alexander; Aarnes, Eva‐Katrine; Lyng, Heidi; Riss, Patrick J.; Malinen, Eirik

doi:10.1007/s00259-019-04375-8

Cited by 15 publications

(10 citation statements)

References 28 publications

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“…GPX4 uses reduced glutathione (composed of glutamate, glycine, and cysteine) to convert phospholipid hydroperoxides to lipid alcohols and inhibits ferroptosis [ 19 ]. Cysteine is the rate-limiting precursor for the synthesis of reduced glutathione [ 20 ]. The cells obtain cysteine through System Xc-, which transfers cystine into the cells and transfers glutamate out of cells in a 1:1 ratio at the same time, and higher contents of glutamate inhibit System Xc- transport, resulting in an increased depletion of cysteine [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Copper Depletion Strongly Enhances Ferroptosis via Mitochondrial Perturbation and Reduction in Antioxidative Mechanisms

Fan

Liu

et al. 2022

Antioxidants

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Copper serves as a co-factor for a host of metalloenzymes, particularly cytochrome c oxidase (COX). Although it is known that impaired COX function can lead to the excessive accumulation of reactive oxygen species (ROS), the mechanisms underlying how copper depletion leads to cell damage are poorly understood. Here, we have investigated the role of copper depletion during ferroptosis. The bathocuproinedisulfonic (BCS) treatment depolarized the mitochondrial membrane potential, increased the total cellular ROS levels, stimulated oxidative stress, and reduced the glutathione levels. Moreover, the depletion of copper limited the protein expression of glutathione peroxidase 4 (GPX4), which is the only enzyme that is known to prevent lipid peroxidation. Furthermore, we found that copper depletion decreased the sensitivity of the dermal papilla cells (DPCs) to erastin (an inducer of ferroptosis), and the ferroptosis inhibitor ferrostatin-1 (Fer-1) partially prevented BCS-mediated cell death. Overall, these findings establish a direct link between copper and ferroptosis; BCS-mediated copper depletion strongly enhances ferroptosis via mitochondrial perturbation and a reduction in antioxidative mechanisms.

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Section: Introductionmentioning

confidence: 99%

Copper Depletion Strongly Enhances Ferroptosis via Mitochondrial Perturbation and Reduction in Antioxidative Mechanisms

Fan

Liu

et al. 2022

Antioxidants

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“…PET data were reconstructed using an OSEM3D‐MAP algorithm to give a dynamic sequence of 17 frames with time resolution 10‐300 seconds and voxel size of 0.87×0.87×0.80 mm 3 , and then analysed using Pmod3.8 software. Following visual inspection of summed images covering the first seven frames of the recording, volumes of interest (2.5‐3.85 mm diameter) were placed in the brain and left kidney of the animals and time activity curves were extracted . Figure shows a summed image of the first seven frames (0‐1 min) and averaged time activity curves for blood, brain and kidney over 30 minutes.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, radiosynthesis, and positron emission tomography neuroimaging using 5‐[¹⁸F]fluoro‐L‐amino suberate

Alluri

Pitman

Malinen

et al. 2019

Labelled Comp Radiopharmac

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System xc‐ (Sxc‐) has emerged as a new biological target for PET studies to detect oxidative and excitotoxic stress. Notably, applications have, thus far, been limited to tumour imaging although Sxc‐) may play a major role in neurodegeneration. The synthesis procedures of tosylate precursor and its translation to Sxc‐ PET tracer 5[18F]fluoro‐L‐amino suberate by manual and automated radiosyntheses are described. A brain‐PET study has been conducted to evaluate the tracer uptake into brain in healthy mice.

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“…The transporter system XC − is also a heterodimer composed of a light chain solute carrier family 7 member 11 (SLC7A11) and a heavy solute carrier family three members 2 (SLC3A2). This transporter system excretes a molecule of cystine whenever a molecule of cystine is taken up into the cell ( Pitman et al, 2019 ). Intracellular cystine is reduced to cysteine mediated by thioredoxin reductase 1 (TXNRD1) ( Mandal et al, 2010 ).…”

Section: Molecular Mechanisms Associated With Ferroptosismentioning

confidence: 99%

Ferroptosis: The Silver Lining of Cancer Therapy

Tang

Huang

et al. 2021

Front. Cell Dev. Biol.

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Regulatory cell death has been a major focus area of cancer therapy research to improve conventional clinical cancer treatment (e.g. chemotherapy and radiotherapy). Ferroptosis, a novel form of regulated cell death mediated by iron-dependent lipid peroxidation, has been receiving increasing attention since its discovery in 2012. Owing to the highly iron-dependent physiological properties of cancer cells, targeting ferroptosis is a promising approach in cancer therapy. In this review, we summarised the characteristics of ferroptotic cells, associated mechanisms of ferroptosis occurrence and regulation and application of the ferroptotic pathway in cancer therapy, including the use of ferroptosis in combination with other therapeutic modalities. In addition, we presented the challenges of using ferroptosis in cancer therapy and future perspectives that may provide a basis for further research.

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Influx rate of 18F-fluoroaminosuberic acid reflects cystine/glutamate antiporter expression in tumour xenografts

Cited by 15 publications

References 28 publications

Copper Depletion Strongly Enhances Ferroptosis via Mitochondrial Perturbation and Reduction in Antioxidative Mechanisms

Copper Depletion Strongly Enhances Ferroptosis via Mitochondrial Perturbation and Reduction in Antioxidative Mechanisms

Synthesis, radiosynthesis, and positron emission tomography neuroimaging using 5‐[¹⁸F]fluoro‐L‐amino suberate

Ferroptosis: The Silver Lining of Cancer Therapy

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Influx rate of 18F-fluoroaminosuberic acid reflects cystine/glutamate antiporter expression in tumour xenografts

Cited by 15 publications

References 28 publications

Copper Depletion Strongly Enhances Ferroptosis via Mitochondrial Perturbation and Reduction in Antioxidative Mechanisms

Copper Depletion Strongly Enhances Ferroptosis via Mitochondrial Perturbation and Reduction in Antioxidative Mechanisms

Synthesis, radiosynthesis, and positron emission tomography neuroimaging using 5‐[18F]fluoro‐L‐amino suberate

Ferroptosis: The Silver Lining of Cancer Therapy

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Synthesis, radiosynthesis, and positron emission tomography neuroimaging using 5‐[¹⁸F]fluoro‐L‐amino suberate