Interdiction of Sphingolipid Metabolism Revisited: Focus on Prostate Cancer

Voelkel‐Johnson, Christina; Norris, James S.; White‐Gilbertson, Shai

doi:10.1016/bs.acr.2018.04.014

Cited by 26 publications

(21 citation statements)

References 141 publications

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“…Also, unsaturated fatty acids e.g., linolenic acid has been identified in association with air long-term air pollution exposure (mainly ultrafine particle (UFP)) that mediated adult onset asthma and cardio-cerebrovascular diseases [23]. We also observed perturbations in sphingolipid metabolism that is involved in inflammation and immunity [46,47] consistent with finding with short-term air pollution [48]. Sphingolipid is also implicated in membrane biology [49] and has been linked to diabetes, hepatocellular carcinoma, and Alzheimer's disease [50,51], heart failure [52], and cancer [47].…”

Section: Discussionmentioning

confidence: 79%

“…We also observed perturbations in sphingolipid metabolism that is involved in inflammation and immunity [46,47] consistent with finding with short-term air pollution [48]. Sphingolipid is also implicated in membrane biology [49] and has been linked to diabetes, hepatocellular carcinoma, and Alzheimer's disease [50,51], heart failure [52], and cancer [47]. We observed perturbations in glutathione metabolism, involved in xenobiotic-mediated oxidative stress [53,54], which has been reported to be associated with traffic-related air pollution [55].…”

Section: Discussionmentioning

confidence: 89%

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Metabolomic signatures of the long-term exposure to air pollution and temperature

et al. 2021

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Background Long-term exposures to air pollution has been reported to be associated with inflammation and oxidative stress. However, the underlying metabolic mechanisms remain poorly understood. Objectives We aimed to determine the changes in the blood metabolome and thus the metabolic pathways associated with long-term exposure to outdoor air pollution and ambient temperature. Methods We quantified metabolites using mass-spectrometry based global untargeted metabolomic profiling of plasma samples among men from the Normative Aging Study (NAS). We estimated the association between long-term exposure to PM2.5, NO2, O3, and temperature (annual average of central site monitors) with metabolites and their associated metabolic pathways. We used multivariable linear mixed-effect regression models (LMEM) while simultaneously adjusting for the four exposures and potential confounding and correcting for multiple testing. As a reduction method for the intercorrelated metabolites (outcome), we further used an independent component analysis (ICA) and conducted LMEM with the same exposures. Results Men (N = 456) provided 648 blood samples between 2000 and 2016 in which 1158 metabolites were quantified. On average, men were 75.0 years and had an average body mass index of 27.7 kg/m2. Almost all men (97%) were not current smokers. The adjusted analysis showed statistically significant associations with several metabolites (58 metabolites with PM2.5, 15 metabolites with NO2, and 6 metabolites with temperature) while no metabolites were associated with O3. One out of five ICA factors (factor 2) was significantly associated with PM2.5. We identified eight perturbed metabolic pathways with long-term exposure to PM2.5 and temperature: glycerophospholipid, sphingolipid, glutathione, beta-alanine, propanoate, and purine metabolism, biosynthesis of unsaturated fatty acids, and taurine and hypotaurine metabolism. These pathways are related to inflammation, oxidative stress, immunity, and nucleic acid damage and repair. Conclusions Using a global untargeted metabolomic approach, we identified several significant metabolites and metabolic pathways associated with long-term exposure to PM2.5, NO2 and temperature. This study is the largest metabolomics study of long-term air pollution, to date, the first study to report a metabolomic signature of long-term temperature exposure, and the first to use ICA in the analysis of both.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 89%

Metabolomic signatures of the long-term exposure to air pollution and temperature

et al. 2021

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“…This phospholipid is mainly involved in aggregation and fusion. It is also assumed to play a significant role in the development of resistance to chemotherapy [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Lipidomics as a Diagnostic Tool for Prostate Cancer

Buszewska-Forajta

Pomastowski

Monedeiro

et al. 2021

Cancers

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The main goal of this study was to explore the phospholipid alterations associated with the development of prostate cancer (PCa) using two imaging methods: matrix-assisted laser desorption ionization with time-of-flight mass spectrometer (MALDI-TOF/MS), and electrospray ionization with triple quadrupole mass spectrometer (ESI-QqQ/MS). For this purpose, samples of PCa tissue (n = 40) were evaluated in comparison to the controls (n = 40). As a result, few classes of compounds, namely phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), sphingomyelins (SMs), and phosphatidylethanolamines (PEs), were determined. The obtained results were evaluated by univariate (Mann–Whitney U-test) and multivariate statistical analysis (principal component analysis, correlation analysis, volcano plot, artificial neural network, and random forest algorithm), in order to select the most discriminative features and to search for the relationships between the responses of these groups of substances, also in terms of the used analytical technique. Based on previous literature and our results, it can be assumed that PCa is linked with both the synthesis of fatty acids and lipid oxidation. Among the compounds, phospholipids, namely PC 16:0/16:1, PC 16:0/18:2, PC 18:0/22:5, PC 18:1/18:2, PC 18:1/20:0, PC 18:1/20:4, and SM d18:1/24:0, were assigned as metabolites with the best discriminative power for the tested groups. Based on the results, lipidomics can be found as alternative diagnostic tool for CaP diagnosis.

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“…Of them, CerS5 and CerS6 predominantly produce C16 ceramide (35). In the prostate, CerS5 is more prevalent than CerS6 (36). Ceramide orchestrates apoptosis, ER stress and autophagy signaling (37,38).…”

Section: Introductionmentioning

confidence: 99%

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

et al. 2021

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Prostate cancer is the second most prevalent malignancy worldwide. In the early stages, the development of prostate cancer is dependent on androgens. Over time with androgen deprivation therapy, 20% of prostate cancers progress to a castration-resistant form. Novel treatments for prostate cancers are still urgently needed. Erianin is a plant-derived bibenzyl compound. We report herein that erianin exhibits anti-tumor effects in androgen-sensitive and castration-resistant prostate cancer cells through different mechanisms. Erianin induces endoplasmic reticulum stress-associated apoptosis in androgen-sensitive prostate cancer cells. It also triggers pro-survival autophagic responses, as inhibition of autophagy predisposes to apoptosis. In contrast, erianin fails to induce apoptosis in castration-resistant prostate cancer cells. Instead, it results in cell cycle arrest at the M phase. Mechanistically, C16 ceramide dictates differential responses of androgen-sensitive and castration-resistant prostate cancer cells to erianin. Erianin elevates C16 ceramide level in androgen-sensitive but not castration-resistant prostate cancer cells. Overexpression of ceramide synthase 5 that specifically produces C16 ceramide enables erianin to induce apoptosis in castration-resistant prostate cancer cells. Our study provides both experimental evidence and mechanistic data showing that erianin is a potential treatment option for prostate cancers.

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Interdiction of Sphingolipid Metabolism Revisited: Focus on Prostate Cancer

Cited by 26 publications

References 141 publications

Metabolomic signatures of the long-term exposure to air pollution and temperature

Metabolomic signatures of the long-term exposure to air pollution and temperature

Lipidomics as a Diagnostic Tool for Prostate Cancer

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

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