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

Cancers, Год журнала: 2024, Номер 16(3), С. 504 - 504

Опубликована: Янв. 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.

Язык: Английский

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

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 993 - 993

Опубликована: Янв. 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

Язык: 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, Год журнала: 2022, Номер 23(7), С. 3652 - 3652

Опубликована: Март 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

Язык: Английский

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The dual role of citrate in cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2023, Номер 1878(6), С. 188987 - 188987

Опубликована: Сен. 17, 2023

Язык: 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, Год журнала: 2024, Номер 291(8), С. 1699 - 1718

Опубликована: Янв. 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.

Язык: Английский

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Role of sodium dependent SLC13 transporter inhibitors in various metabolic disorders

Molecular and Cellular Biochemistry, Год журнала: 2022, Номер 478(8), С. 1669 - 1687

Опубликована: Дек. 10, 2022

Язык: Английский

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

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Март 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.

Язык: Английский

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Opportunities and Challenges for Inhibitors Targeting Citrate Transport and Metabolism in Drug Discovery

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(14), С. 9229 - 9250

Опубликована: Июль 10, 2023

Lipid metabolism disorder is closely related to metabolic diseases, inflammation, and cancer. The concentration of citrate in the cytosol has a significant impact on lipid synthesis. expression transporters (SLC13A5 SLC25A1) enzymes (ACLY) proves be substantially raised various diseases disorders metabolism, such as hyperlipemia, nonalcoholic fatty liver disease, prostate Targeting key proteins transport pathways considered an effective strategy for treating diseases. However, there currently only one ACLY inhibitor approved marketing, no SLC13A5 entered clinical research. Further development drugs targeting needed treatment This perspective summarizes biological role, therapeutic potential, research progress then discusses achievements prospects modulators applications.

Язык: Английский

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Why and how citrate may sensitize malignant tumors to immunotherapy

Drug Resistance Updates, Год журнала: 2024, Номер 78, С. 101177 - 101177

Опубликована: Ноя. 26, 2024

Язык: Английский

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

Cancers, Год журнала: 2025, Номер 17(3), С. 553 - 553

Опубликована: Фев. 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.

Язык: Английский

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