Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(3)

Published: March 1, 2024

Abstract Heightened lactate production in cancer cells has been linked to various cellular mechanisms such as angiogenesis, hypoxia, macrophage polarisation and T‐cell dysfunction. The lactate‐induced lactylation of histone lysine residues is noteworthy, it functions an epigenetic modification that directly augments gene transcription from chromatin. This originating effectively fosters a reliance on transcription, thereby expediting tumour progression development. Herein, this review explores the correlation between characteristics, revealing innovative process enhances vulnerability malignancy. Moreover, imperative acknowledge paramount importance acknowledging therapeutic methodologies for proficiently managing by precisely targeting signalling. comprehensive illuminates crucial yet inadequately investigated aspect lactylation, providing valuable insights into its clinical ramifications prospective interventions centred lactylation.

Language: Английский

---

Metabolic regulation of neutrophil functions in homeostasis and diseases

Journal of Leukocyte Biology, Journal Year: 2024, Volume and Issue: 116(3), P. 456 - 468

Published: March 7, 2024

Neutrophils are the most abundant leukocytes in humans and play a role innate immune response by being first cells attracted to site of infection. While early studies presented neutrophils as almost exclusively glycolytic cells, recent advances show that these use several metabolic pathways other than glycolysis, such pentose phosphate pathway, oxidative phosphorylation, fatty acid oxidation, glutaminolysis, which they modulate perform their functions. Metabolism shifts from oxidation-mediated mitochondrial respiration immature glycolysis mature neutrophils. Tissue environments largely influence neutrophil metabolism according nutrient sources, inflammatory mediators, oxygen availability. Inhibition results impairment certain effector functions, NETosis, chemotaxis, degranulation, reactive species generation. Alteration functions is implicated human diseases, antiphospholipid syndrome, coronavirus disease 2019, bronchiectasis. Metabolic regulators AMPK, HIF-1α, mTOR, Arf6 linked function could potentially be targeted for treatment diseases associated with dysfunction. This review details effects alterations on cells.

Language: Английский

---

Combination of Low-Dose Sulforaphane and Docetaxel on Mitochondrial Function and Metabolic Reprogramming in Prostate Cancer Cell Lines

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1013 - 1013

Published: Jan. 24, 2025

Considering the limitations of monotherapies due to chemoresistance and side effects, this research aimed determine whether low doses sulforaphane (SFN) combined with docetaxel (DCT) could enhance therapeutic efficacy. Prostate cancer cell lines LNCaP PC-3 were treated individual IC50 SFN DCT half-reduced values for SFN:DCT combination. Metabolic markers, including glucose consumption, lactate production, reactive oxygen species (ROS), mitochondrial mass, caspase activity, assessed. In cells, combination reduced viability 50%, comparable monotherapy (48%). Caspase 3 activation was also higher (2.4 ± 0.75 RFU) than alone (2.1 0.47 RFU), while 8 remained comparable, indicating equivalent effectiveness at lower concentrations. induced (1.16 0.0484 levels slightly (1.51 0.2062 but achieved greater reductions in reflecting its ability target metabolic vulnerabilities aggressive phenotypes. Our findings suggest that is a promising strategy early-stage prostate cancer. By achieving efficacy doses, maintains impact, mitigating adverse effects conventional treatment.

Language: Английский

---

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

---

Hypoxia signaling in cancer: HIF-1α stimulated by COVID-19 can lead to cancer progression and chemo-resistance in oral squamous cell carcinoma (OSCC)

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 26, 2025

Language: Английский

---

Tumor Acidity as a Result of the Warburg Effect in Cancer Glucose Metabolism and Its Role in Cancer Progression—A Review

Military Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

ABSTRACT Introduction Resistance to cancer treatment, metastases, and rapid progression remain overwhelming factors for patients, their families, health providers. One of the key mechanisms invasiveness malignancy has been identified be tumor acidity as a direct result Warburg effect observed during continuous formation cancerous tissue. This study describes in etiology, which causes lower pH levels tumors compared healthy tissues, it also discusses impact on damage tissue while facilitating invasion dissemination. Materials Methods A review literature was conducted using search words such as: “Tumor acidity,” “Cancer metabolism,” “Warburg effect,” “Glucose cells,” analyze tissue, well potential progression. Results The showed high level suggestive evidence negative It furthermore confirmed some suspected ways induced by acidity. Conclusions Cancer is associated with massive complex metabolic reprogramming resulting acidity, further induce However, presents vulnerability that can used drug target help enhance efficiency conventional therapies.

Language: Английский

---

Repurposing Antiepileptic Drugs for Cancer: A Promising Therapeutic Strategy

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(8), P. 2673 - 2673

Published: April 14, 2025

Epilepsy is a neurological disorder characterized by repeated convulsions. Antiepileptic drugs (AEDs) are the main course of therapy for epilepsy. These medications given according to each patient’s personal medical history and types seizures they suffer. They have been employed decades manage epilepsy, thus delivering relief from through numerous mechanisms action. Aside their anticonvulsant attributes, current evidence suggests that certain AEDs may display potential inhibitory effects against cancer invasion metastasis. This review explored complicated interactions between modes action pathways causing cancer, impact on metastasis various forms while addressing associated side effects. For example, valproic acid inhibits histone deacetylase, hyperacetylation genes, especially those regulating cell cycle, culminating in cycle arrest. Topiramate carbonic anhydrase, disrupting acidic microenvironment needed cells thrive. Lacosamide increases slow inactivation voltage gated Na+ channel, inhibiting growth, proliferation, many cancers. Although drug development complex task due regulatory, intellectual property, economic challenges, researchers exploring repurposing tactics overcome these challenges find new therapeutic alternatives diseases like cancer. Thus, considered among most effective ways develop candidates using novel properties characteristics, this also discusses issues.

Language: Английский

---

Nanomaterials in cancer starvation therapy: pioneering advances, therapeutic potential, and clinical challenges

Cancer and Metastasis Reviews, Journal Year: 2025, Volume and Issue: 44(2)

Published: May 10, 2025

Language: Английский

---

Metabolic Landscape of Osteosarcoma: Reprogramming of Lactic Acid Metabolism and Metabolic Communication

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(2)

Published: Feb. 22, 2024

Background: Lactic acid, previously regarded only as an endpoint of glycolysis, has emerged a major regulator tumor invasion, growth, and the microenvironment. In this study, we aimed to explore reprogramming lactic acid metabolism relevant osteosarcoma (OS) microenvironment by decoding underlying metabolic landscape OS cells intercellular signaling alterations. Methods: The was evaluated using single-cell gene expression data, clustering, screening hub genes in samples transcriptome data. role NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 6 (NDUFAF6) validated with vitro studies patient experiments. Results: Single-cell RNA sequencing data metabolismhigh subcluster OS. Further investigation communications revealed unique communication pattern between other subclusters. Next, two phenotypes were defined, six metabolism-related (LRGs), including biomarker NDUFAF6, screened experiments confirmed that NDUFAF6 is crucial metabolism-associated Conclusions: patterns suggested (TME) identified LRG prognostic biomarker.

Language: Английский

---

GPR68 supports AML cells through the calcium/calcineurin pro-survival pathway and confers chemoresistance by mediating glucose metabolic symbiosis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1871(1), P. 167565 - 167565

Published: Nov. 8, 2024

Language: Английский

---