Metabolic Signature of Warburg Effect in Cancer: An Effective and Obligatory Interplay between Nutrient Transporters and Catabolic/Anabolic Pathways to Promote Tumor Growth

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 504 - 504

Published: Jan. 24, 2024

Aerobic glycolysis in cancer cells, originally observed by Warburg 100 years ago, which involves the production of lactate as end product glucose breakdown even presence adequate oxygen, is foundation for current interest cancer-cell-specific reprograming metabolic pathways. The renewed cell metabolism has now gone well beyond original effect related to other pathways that include amino acid metabolism, one-carbon pentose phosphate pathway, nucleotide synthesis, antioxidant machinery, etc. Since and acids constitute primary nutrients fuel altered transporters mediate transfer these their metabolites not only across plasma membrane but also mitochondrial lysosomal membranes have become an integral component expansion effect. In this review, we focus on interplay between facilitates reprogramming, a hallmark cells. beneficial outcome recent understanding unique signature surrounding identification novel drug targets development new generation therapeutics treat cancer.

Language: Английский

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Exploring the Link Between Telomeres and Mitochondria: Mechanisms and Implications in Different Cell Types

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 993 - 993

Published: Jan. 24, 2025

Telomeres protect chromosome ends from damage, but they shorten with each cell division due to the limitations of DNA replication and are further affected by oxidative stress. This shortening is a key feature aging, telomerase, an enzyme that extends telomeres, helps mitigate this process. Aging also associated mitochondrial dysfunction, leading increased reactive oxygen species (ROS) exacerbate cellular damage promote apoptosis. Elevated ROS levels can telomeres oxidizing guanine disrupting their regulation. Conversely, telomere impacts function, activation telomerase has been shown reverse decline. A critical link between dysfunction response, which activates tumor suppressor protein p53, resulting in reduced biogenesis metabolic disruptions. highlights bidirectional relationship maintenance function. review explores complex interactions mitochondria across various types, fibroblasts sperm cells, shedding light on interconnected mechanisms underlying aging

Language: Английский

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Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3652 - 3652

Published: March 26, 2022

Recent mouse model experiments support an instrumental role for senescent cells in age-related diseases and may be causal to certain pathologies. A strongly supported hypothesis is that extranuclear chromatin recognized by the cyclic GMP-AMP synthase-stimulator of interferon genes pathway, which turn leads induction several inflammatory cytokines as part senescence-associated secretory phenotype. This sterile inflammation increases with chronological age age-associated disease. More recently, intracellular extracellular metabolic changes have been described but it not clear whether any them functional significance. In this review, we highlight potential effect dietary metabolites modulation phenotype addition discussing how experimental conditions influence cell metabolism, especially energy regulation. Finally, citrate accumulates following types senescence, focus on recently reported aging We propose active component via its intake through diet even contribute cause

Language: Английский

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Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high‐fat diet

FEBS Journal, Journal Year: 2024, Volume and Issue: 291(8), P. 1699 - 1718

Published: Jan. 20, 2024

Over the years, pancreatic cancer has experienced a global surge in incidence and mortality rates, largely attributed to influence of obesity diabetes mellitus on disease initiation progression. In this study, we investigated pathogenesis mice subjected high-fat diet (HFD) observed an increase citric acid expenditure. Notably, citrate treatment demonstrates significant efficacy promoting tumor cell apoptosis, suppressing proliferation, inhibiting growth vivo. Our investigations revealed that achieved these effects by releasing secreted protein acidic rich cysteine (SPARC) proteins, repolarizing M2 macrophages into M1 macrophages, facilitating apoptosis. Overall, our research highlights critical role as pivotal metabolite intricate relationship between cancer. Furthermore, uncovered metabolic immune checkpoint function SPARC cancer, suggesting its potential both biomarker therapeutic target treating patient population.

Language: Английский

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The dual role of citrate in cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(6), P. 188987 - 188987

Published: Sept. 17, 2023

Language: Английский

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Metabolic responses to the occurrence and chemotherapy of pancreatic cancer: biomarker identification and prognosis prediction

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 23, 2024

Abstract As the most malignant tumor, prognosis of pancreatic cancer is not ideal even in small number patients who can undergo radical surgery. a highly heterogeneous chemotherapy resistance major factor leading to decreased efficacy and postoperative recurrence cancer. In this study, nuclear magnetic resonance (NMR)-based metabolomics was applied identify serum metabolic characteristics ductal adenocarcinoma (PDAC) screen potential biomarkers for its diagnosis. Metabolic changes with different CA19-9 levels during were also monitored compared differential metabolites that may affect chemotherapy. Finally, 19 screened serve diagnosis PDAC, significant differences between two stratifications PDAC involved energy metabolism, lipid amino acid citric metabolism. Enrichment analysis pathways revealed six shared by such as alanine, aspartate glutamate arginine biosynthesis, glutamine citrate cycle, pyruvate glycogolysis/gluconeogeneis. The similarity responses provided reference clinical prediction benefits patients.

Language: Английский

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Role of sodium dependent SLC13 transporter inhibitors in various metabolic disorders

Molecular and Cellular Biochemistry, Journal Year: 2022, Volume and Issue: 478(8), P. 1669 - 1687

Published: Dec. 10, 2022

Language: Английский

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Untargeted Metabolomics and Liquid Biopsy Investigation of Circulating Biomarkers in Soft Tissue Sarcoma

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 553 - 553

Published: Feb. 6, 2025

Background: Soft tissue sarcomas (STSs) are rare, highly malignant mesenchymal tumours, comprising approximately 1% of all adult cancers and about 15% paediatric solid tumours. STSs exhibit considerable genomic complexity with diverse subtypes, posing significant clinical challenges. Objectives: This study aims to characterise the molecular signature primary STS through liquid biopsies untargeted metabolomic profiling 75 patients, providing deep insights into cellular processes potential therapeutic targets. Methods: analysed serum samples using nuclear magnetic resonance (NMR) spectroscopy for profiling. Multivariate data analysis machine learning classifiers were employed identify biomarkers. Results: A panel eleven deregulated metabolites discovered in patients STS, implications cancer diagnosis treatment. Conclusions: Choline decrease emerged as a marker progression, highlighting targeting its metabolism approaches STS. The NMR protocol proved effective determining circulating biomarkers from biopsies, making it suitable rare disease research.

Language: Английский

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Serum Metabolomics Profiling Coupled with Machine Learning Identifies Potential Diagnostic and Prognostic Candidate Markers in Meningioma Using Raman Spectroscopy, ATR-FTIR, and LC–MS/MS

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Meningioma, the most prevalent brain tumor, poses significant challenges due to its unclear transition from low-grade aggressive forms, with limited knowledge about grade-specific markers. We have utilized vibrational spectroscopic techniques such as ATR-FTIR and Raman spectroscopy, alongside LC-MS/MS-based mass spectrometry understand systemic cues evaluate them for clinical practice. The acquired spectra of 46 meningioma patients (27 19 high-grade) 8 healthy individuals revealed 98.15% 83.33% accuracy based on PC-LDA. grade classification an around 70%, implying presence subtypes phases. observed alterations corresponded lipids, nucleic acids, proteins. Further, study identified different derivatives cholines, indoles, sphingosine, tryptophan, their respective metabolic pathways contributors in tumorigenesis progression. PRM-based targeted validation feature selection was carried out 43 17 controls. Glycochenodeoxycholic acid, indole-3-acetic trans-3-indoleacrylic glycodeoxycholic 5α-dihydrotestosteroneglucornide, glycocholic acid segregated samples 90% while features like stercobilin, sphingosine-1-phosphate, deoxycholic citric could classify grades 70% accuracy. These findings suggest that further across larger cohorts enhance usage settings.

Language: Английский

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Cell-Free DNA (cfDNA) Regulates Metabolic Remodeling in the ES-2 Ovarian Carcinoma Cell Line, Influencing Cell Proliferation, Quiescence, and Chemoresistance in a Cell-of-Origin-Specific Manner

Metabolites, Journal Year: 2025, Volume and Issue: 15(4), P. 244 - 244

Published: April 2, 2025

Background: The cell-free DNA (cfDNA) is an extracellular fragmented found in body fluids physiological and pathophysiological contexts. In cancer, cfDNA has been pointed out as a marker for disease diagnosis, staging, prognosis; however, little known about its biological role. Methods: role of released by ES-2 ovarian cancer cells was investigated, along with the impact glucose bioavailability culture duration cfDNA-induced phenotype. effect on cell proliferation evaluated curves, migration assessed through wound healing. We explored different variants cells’ metabolic profile using nuclear magnetic resonance (NMR) spectroscopy cisplatin resistance flow cytometry. Moreover, we protein levels DNA-sensitive Toll-like receptor 9 (TLR9) immunofluorescence colocalization lysosome-associated membrane 1 (LAMP1). Results: This study demonstrated that despite inducing similar effects, promote effects derived from line. observed instant reactions adopting brings back functioning more favorable conditions supporting resembling origin variant, unselected cells. However, long-term selective factor, certain induced quiescence favors chemoresistance subset Conclusions: Therefore, tumoral microenvironments may generate will differently, orchestrating fate.

Language: Английский

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