Accumulated cholesterol protects tumours from elevated lipid peroxidation in the microenvironment

Zhao, Xi; Lian, Xinyu; Xie, Junbo; Liu, G.

doi:10.1016/j.redox.2023.102678

Cited by 34 publications

(21 citation statements)

References 44 publications

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“…Interestingly, the ratio of cholesterol to phosphocholine fragments ( I 386.6 / I 184.1 ) showed a significant upregulation trend in cancer cells (Figure e), indicating a higher expression of cholesterol than in normal cells. Cholesterol, as one of the main components of cell membranes, can regulate many properties of cell membranes. , It has been reported that a high level of membrane cholesterol can decrease cell stiffness to facilitate malignant transformation and tumor progression. , Our results intuitively confirmed the high expression of cholesterol on the cancer cell membranes at the molecular level and revealed a potential target to improve the effectiveness of cancer therapies. The above results implied a bright application prospect of our current method in the omic analysis of cell membranes.…”

Section: Results and Disscussionsupporting

confidence: 75%

“…54,55 It has been reported that a high level of membrane cholesterol can decrease cell stiffness to facilitate malignant transformation and tumor progression. 56,57 Our results intuitively confirmed the high expression of cholesterol on the cancer cell membranes at the molecular level and revealed a potential target to improve the effectiveness of cancer therapies. The above results implied a bright application prospect of our current method in the omic analysis of cell membranes.…”

Section: Workflow and Key Configuration Of The Instrumentsupporting

confidence: 66%

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Nanometer Resolution Mass Spectro-Microtomography for In-Depth Anatomical Profiling of Single Cells

et al. 2023

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Visually identifying the molecular changes in single cells is of great importance for unraveling fundamental cellular functions as well as disease mechanisms. Herein, we demonstrated a mass spectro-microtomography with an optimal voxel resolution of ∼300 × 300 × 25 nm3, which enables three-dimensional tomography of chemical substances in single cells. This mass imaging method allows for the distinguishment of abundant endogenous and exogenous molecules in subcellular structures. Combined with statistical analysis, we demonstrated this method for spatial metabolomics analysis of drug distribution and subsequent molecular damages caused by intracellular drug action. More interestingly, thanks to the nanoprecision ablation depth (∼12 nm), we realized metabolomics profiling of cell membrane without the interference of cytoplasm and improved the distinction of cancer cells from normal cells. Our current method holds great potential to be a powerful tool for spatially resolved single-cell metabolomics analysis of chemical components during complex biological processes.

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Section: Results and Disscussionsupporting

confidence: 75%

Section: Workflow and Key Configuration Of The Instrumentsupporting

confidence: 66%

Nanometer Resolution Mass Spectro-Microtomography for In-Depth Anatomical Profiling of Single Cells

et al. 2023

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“…The decreased levels of CE might be interpreted as an increase of CE hydrolysis in cell lipid droplets as an adaptation response to the presence of stressing chemicals, leading to an increase of free cholesterol levels. A recent publication demonstrated that free cholesterol protects against lipid peroxidation (produced by the interaction of ROS with lipids) through decreasing plasma membrane fluidity in A549 cells . In agreement with this protective role, elevated cholesterol levels have been previously observed in etoposide-resistant A549 cells .…”

Section: Resultssupporting

confidence: 60%

“…This mixture promoted both IL-8 release and ROS production and was unrelated to cell death induction. As previously mentioned, CE hydrolysis can be interpreted as a survival response to release free cholesterol and counterbalance the lipid peroxidation produced by ROS . Apart from the presence of PCB compounds in these three chemical profiles, they also had in common the presence of 4,4′-DDT or the 4,4′-DDE derivative as important contributors.…”

Section: Resultsmentioning

confidence: 89%

Effects of Indoor Dust Exposure on Lung Cells: Association of Chemical Composition with Phenotypic and Lipid Changes in a 3D Lung Cancer Cell Model

Pyambri,

Lacorte,

Jaumot

et al. 2023

Environ. Sci. Technol.

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Indoor dust is a key contributor to the global human exposome in urban areas since the population develops most of its activities in private and public buildings. To gain insight into the health risks associated with this chronic exposure, it is necessary to characterize the chemical composition of dust and understand its biological impacts using reliable physiological models. The present study investigated the biological effects of chemically characterized indoor dust extracts using three-dimensional (3D) lung cancer cell cultures combining phenotypic and lipidomic analyses. Apart from the assessment of cell viability, reactive oxygen species (ROS) induction, and interleukin-8 release, lipidomics was applied to capture the main lipid changes induced as a cellular response to the extracted dust compounds. The application of chemometric tools enabled the finding of associations between chemical compounds present in dust and lipidic and phenotypic profiles in the cells. This study contributes to a better understanding of the toxicity mechanisms associated with exposure to chemical pollutants present in indoor dust.

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“…Alternatively, different cells (LSCs and HT1080 cells in this case) may have distinct responses to the same stimulation, as has been shown by others 40 . In another work, cholesterol was shown to decrease membrane fluidity and promote lipid raft formation, thereby restraining lipid peroxidation in cancer cells 41 . Interestingly, we also observed SQLE independent effect in HT1080 cells, where cells were supplemented with 60µM instead of 50µM cholesterol, suggesting other pathways taking effect at high cholesterol concentration.…”

Section: Discussionmentioning

confidence: 98%

Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene

Sun¹,

Liu²,

Cui³

et al. 2023

Preprint

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Recent findings have shown that fatty acid metabolism is profoundly involved in ferroptosis. However, the role of cholesterol in this process remains incompletely understood. In this work, we show that modulating cholesterol levels changes vulnerability of cells to ferroptosis. Cholesterol alters metabolic flux of the mevalonate pathway by promoting Squalene Epoxidase (SQLE) degradation, a rate limiting step in cholesterol biosynthesis, thereby increasing both CoQ10 and squalene levels. Importantly, whereas inactivation of Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), the branch point of cholesterol biosynthesis pathway, exhibits minimal effect on ferroptosis, simultaneous inhibition of both CoQ10 and squalene biosynthesis completely abrogates the effect of cholesterol. Mouse models of ischemia-reperfusion and doxorubicin induced hepatoxicity confirms the protective role of cholesterol in ferroptosis. Our study elucidates a potential role of ferroptosis in diseases related to dysregulation of cholesterol metabolism and suggests a new possible therapeutic target that involve ferroptotic cell death.

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Accumulated cholesterol protects tumours from elevated lipid peroxidation in the microenvironment

Cited by 34 publications

References 44 publications

Nanometer Resolution Mass Spectro-Microtomography for In-Depth Anatomical Profiling of Single Cells

Nanometer Resolution Mass Spectro-Microtomography for In-Depth Anatomical Profiling of Single Cells

Effects of Indoor Dust Exposure on Lung Cells: Association of Chemical Composition with Phenotypic and Lipid Changes in a 3D Lung Cancer Cell Model

Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene

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