NAD+ metabolism, stemness, the immune response, and cancer

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Jan. 1, 2021

NAD+ was discovered during yeast fermentation, and since its discovery, important roles in redox metabolism, aging, longevity, the immune system DNA repair have been highlighted. A deregulation of levels has associated with metabolic diseases aging-related diseases, including neurodegeneration, defective responses, cancer. acts as a cofactor through interplay NADH, playing an essential role many enzymatic reactions energy such glycolysis, oxidative phosphorylation, fatty acid oxidation, TCA cycle. also plays deacetylation by sirtuins ADP ribosylation damage/repair PARP proteins. Finally, different NAD hydrolase proteins consume while converting it into ADP-ribose or cyclic counterpart. Some these proteins, CD38, seem to be extensively involved response. Since cannot taken directly from food, metabolism is essential, NAMPT key enzyme recovering nicotinamide generating most cellular pools. Because complex network pathways which enzyme, NAMPT, cancer understandable. In present work, we review ways that they may influence system, stemness, some ongoing research on therapeutic approaches.

Language: Английский

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Relevance of SIRT1-NF-κB Axis as Therapeutic Target to Ameliorate Inflammation in Liver Disease

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(11), P. 3858 - 3858

Published: May 29, 2020

Inflammation is an adaptive response in pursuit of homeostasis reestablishment triggered by harmful conditions or stimuli, such as infection tissue damage. Liver diseases cause approximately 2 million deaths per year worldwide and hepatic inflammation a common factor to all them, being the main driver damage causing progression from non-alcoholic fatty liver disease (NAFLD) steatohepatitis (NASH), cirrhosis and, ultimately, hepatocellular carcinoma (HCC). The metabolic sensor SIRT1, class III histone deacetylase with strong expression tissues liver, transcription NF-κB, master regulator inflammatory response, show antagonistic relationship controlling inflammation. For this reason, SIRT1 targeting emerging potential strategy improve different and/or pathologies. In review, we explore diverse upstream regulators some natural/synthetic activators possible therapeutic treatment for diseases.

Language: Английский

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Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole

Molecules, Journal Year: 2018, Volume and Issue: 23(12), P. 3361 - 3361

Published: Dec. 18, 2018

Compounds containing 1,3,4-oxadiazole ring in their structure are characterised by multidirectional biological activity. Their anti-proliferative effects associated with various mechanisms, such as inhibition of growth factors, enzymes, kinases and others, deserve attention. The activity these compounds was tested on cell lines cancers. In most publications, the active derivatives exceeded effect reference drugs, so they may become main new anti-cancer drugs future.

Language: Английский

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Cytotoxicity of ungeremine towards multi-factorial drug resistant cancer cells and induction of apoptosis, ferroptosis, necroptosis and autophagy

Phytomedicine, Journal Year: 2019, Volume and Issue: 60, P. 152832 - 152832

Published: Jan. 15, 2019

Language: Английский

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The Role of Nicotinamide in Cancer Chemoprevention and Therapy

Biomolecules, Journal Year: 2020, Volume and Issue: 10(3), P. 477 - 477

Published: March 20, 2020

Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and precursor nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production adenosine triphosphate (ATP), NAD+ acts as substrate several enzymes including sirtuin 1 (SIRT1) poly ADP-ribose polymerase (PARP1). Notably, NAM an inhibitor both SIRT1 PARP1. Accumulating evidence suggests that plays cancer prevention therapy. Phase III clinical trials have confirmed efficacy non-melanoma skin chemoprevention or adjunct to radiotherapy against head neck, laryngeal, urinary bladder cancers. Evidence other cancers has mostly been collected through preclinical research and, majority, not yet evidence-based. potential safe, well-tolerated, cost-effective agent be used However, more studies are needed fully unravel value.

Language: Английский

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Post-translational Control of RNA-Binding Proteins and Disease-Related Dysregulation

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: April 27, 2021

Cell signaling mechanisms modulate gene expression in response to internal and external stimuli. Cellular adaptation requires a precise coordinated regulation of the transcription translation processes. The post-transcriptional control mRNA metabolism is mediated by so-called RNA-binding proteins (RBPs), which assemble with specific transcripts forming messenger ribonucleoprotein particles highly dynamic composition. RBPs constitute class trans -acting regulatory affinity for certain consensus elements present molecules. However, these regulators are subjected post-translational modifications (PTMs) that constantly adjust their activity maintain cell homeostasis. PTMs can dramatically change subcellular localization, binding RNA protein partners, turnover rate RBPs. Moreover, ability many undergo phase transition and/or recruitment previously formed membrane-less organelles, such as stress granules, also regulated PTMs. Interestingly, dysregulation has been associated pathophysiology different diseases. Abnormal PTM patterns lead distortion physiological role due mislocalization, loss or gain function, accelerated disrupted degradation. This Mini Review offers broad overview selected involvement neurodegenerative disorders, cancer other pathologies.

Language: Английский

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Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 228, P. 116174 - 116174

Published: March 27, 2024

Language: Английский

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Nicotinamide Adenine Dinucleotide (NAD) Metabolism as a Relevant Target in Cancer

Cells, Journal Year: 2022, Volume and Issue: 11(17), P. 2627 - 2627

Published: Aug. 24, 2022

NAD+ is an important metabolite in cell homeostasis that acts as essential cofactor oxidation–reduction (redox) reactions various energy production processes, such the Krebs cycle, fatty acid oxidation, glycolysis and serine biosynthesis. Furthermore, high levels are required since they also participate many other nonredox molecular DNA repair, posttranslational modifications, signalling, senescence, inflammatory responses apoptosis. In these reactions, ADP-ribose donor for enzymes sirtuins (SIRTs), poly-(ADP-ribose) polymerases (PARPs) cyclic (cADPRs). Therefore, to meet both redox demands, tumour cells must maintain levels, enhancing their synthesis mainly through salvage pathway. NAMPT, rate-limiting enzyme of this pathway, has been identified oncogene some cancer types. Thus, NAMPT proposed a suitable target therapy. inhibition causes depletion content cell, leading ATP synthesis. This effect can cause decrease proliferation death, by recent years, specific inhibitors have developed, them currently clinical trials. Here we review NAD metabolism therapy target.

Language: Английский

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G-quadruplexes in cancer-related gene promoters: from identification to therapeutic targeting

Expert Opinion on Therapeutic Patents, Journal Year: 2023, Volume and Issue: 33(11), P. 745 - 773

Published: Oct. 19, 2023

ABSTRACTIntroduction Guanine-rich DNA sequences can fold into four-stranded noncanonical secondary structures called G-quadruplexes (G4s) which are widely distributed in functional regions of the human genome, such as telomeres and gene promoter regions. Compelling evidence suggests their involvement key genome functions expression stability. Notably, abundance G4-forming near transcription start sites potential regulating oncogenes.Areas covered This review provides an overview current knowledge on G4s oncogene promoters. The most representative G4-binding ligands have also been documented. objective this work is to present a comprehensive promising targets for development novel highly specific anticancer drugs capable selectively impacting individual or limited number genes.Expert opinion Modulation G4 formation by has proposed powerful new tool treat cancer through control expression. Actually, small molecules seem simultaneously target range G4s, potentially influencing several critical driver genes cancer, thus producing significant therapeutic benefits.KEYWORDS: CancerDNA G-quadruplexG-quadruplex binding proteinsG-quadruplex ligandsG-quadruplex structuresgene promotersoncogenespatents Article highlights promoters.Evidence G-quadruplex regulation establishing connections biology.The role cellular processes make these intervention cancer.This update promoters together with ligands, specifically designed modulate expression.Declaration interestThe authors no relevant affiliations financial any organization entity interest conflict subject matter materials discussed manuscript. includes employment, consultancies, honoraria, stock ownership options, expert testimony, grants patents received pending, royalties.Reviewer disclosuresPeer reviewers manuscript other relationships disclose.Additional informationFundingThis was supported Italian Association Cancer Research (IG 26313 A.R. IG 24590 B.P.).

Language: Английский

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CD4 ⁺ FOXP3Exon2 ⁺ regulatory T cell frequency predicts breast cancer prognosis and survival

Science Advances, Journal Year: 2025, Volume and Issue: 11(3)

Published: Jan. 15, 2025

CD4 + FOXP3 regulatory T cells (T regs ) suppress immune responses to tumors, and their accumulation in the tumor microenvironment (TME) correlates with poor clinical outcome several cancers, including breast cancer (BC). However, properties of intratumoral remain largely unknown. Here, we found that a functionally distinct subpopulation , expressing Exon2 splicing variants, is prominent patients hormone receptor–positive BC prognosis. Notably, comprehensive examination TCGA validated FOXP3E2 as an independent prognostic marker all other subtypes. We expression underlies BCs defective mismatch repair stem-like signature highlights pathways involved survival. Last, TME induces through CXCL12/CXCR4 axis confirmed higher immunosuppressive capacity derived from BC. Our study suggests might be used biomarker predict prognosis survival develop super-targeted immunotherapies.

Language: Английский

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