Targeting metabolism to influence cellular senescence a promising anti-cancer therapeutic strategy DOI Creative Commons

Zehua Wang,

Jianwen Gao, Congjian Xu

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 116962 - 116962

Опубликована: Июнь 26, 2024

Metabolic disorders are considered the hallmarks of cancer and metabolic reprogramming is emerging as a new strategy for treatment. Exogenous endogenous stressors can induce cellular senescence; interactions between senescence systemic metabolism dynamic. Cellular disrupts homeostasis in various tissues, which further promotes senescence, creating vicious cycle facilitating tumor occurrence, recurrence, altered outcomes anticancer treatments. Therefore, regulation related secretory phenotypes breakthrough therapy; moreover, proteins involved associated pathways prospective therapeutic targets. Although studies on association tumors have emerged recent years, elucidation this complex correlation required comprehensive knowledge. In paper, we review research progress cell aging metabolism, focusing strategies targeting to modulate relevant context anti-tumor therapy. Finally, discuss significance improving specificity safety anti-senescence drugs, potential challenge

Язык: Английский

Targeting methionine metabolism in cancer: opportunities and challenges DOI
Peng Bin, Chuanlong Wang, Hangchao Zhang

и другие.

Trends in Pharmacological Sciences, Год журнала: 2024, Номер 45(5), С. 395 - 405

Опубликована: Апрель 5, 2024

Язык: Английский

Процитировано

15
Role of Folate in Liver Diseases DOI Open Access
Minlan Yang,

Dingye Wang,

Xiyuan Wang

и другие.

Nutrients, Год журнала: 2024, Номер 16(12), С. 1872 - 1872

Опубликована: Июнь 14, 2024

Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines one essential vitamins for human growth reproduction. deficiency due to low dietary intake, poor absorption folate, alterations folate metabolism genetic defects or drug interactions significantly increases risk diseases such as neural tube defects, cardiovascular disease, cancer, cognitive dysfunction. Recent studies have shown that can cause hyperhomocysteinemia, which hypertension high homocysteine levels are an independent factor liver fibrosis cirrhosis. In addition, results increased secretion pro-inflammatory factors impaired lipid liver, leading accumulation hepatocytes fibrosis. There substantial evidence contributes development progression variety diseases, including non-alcoholic fatty disease (NAFLD), steatohepatitis (NASH), alcoholic (ALD), viral hepatitis, hepatic fibrosis, cancer. Here we review key on role pathophysiology summarize current status treatment speculate may be potential therapeutic target diseases.

Язык: Английский

Процитировано

11
Building a translational cancer dependency map for The Cancer Genome Atlas DOI Creative Commons
Xu Shi, Christos Gekas, Daniel Verduzco

и другие.

Nature Cancer, Год журнала: 2024, Номер 5(8), С. 1176 - 1194

Опубликована: Июль 15, 2024

Cancer dependency maps have accelerated the discovery of tumor vulnerabilities that can be exploited as drug targets when translatable to patients. The Genome Atlas (TCGA) is a compendium 'maps' detailing genetic, epigenetic and molecular changes occur during pathogenesis cancer, yet it lacks map translate gene essentiality in patient tumors. Here, we used machine learning build translational for tumors, which identified predict responses disease outcomes. A similar approach was tolerability healthy tissues prioritize with best therapeutic windows. subset patient-translatable synthetic lethalities were experimentally tested, including PAPSS1/PAPSS12 CNOT7/CNOT78, validated vitro vivo. Notably, PAPSS1 lethality driven by collateral deletion PAPSS2 PTEN correlated survival. Finally, provided web-based application exploring vulnerabilities.

Язык: Английский

Процитировано

10
Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases DOI
Zeming Wu, Jing Qu, Guang‐Hui Liu

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 25(12), С. 979 - 1000

Опубликована: Окт. 3, 2024

Язык: Английский

Процитировано

8
Interactions between the metabolic reprogramming of liver cancer and tumor microenvironment DOI Creative Commons

Haoqiang Yang,

Jinghui Li, Yuanjie Niu

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 14, 2025

Metabolic reprogramming is one of the major biological features malignant tumors, playing a crucial role in initiation and progression cancer. The tumor microenvironment consists various non-cancer cells, such as hepatic stellate cancer-associated fibroblasts (CAFs), immune well extracellular matrix soluble substances. In liver cancer, metabolic not only affects its own growth survival but also interacts with other cells by influencing expression release metabolites cytokines (such lactate, PGE2, arginine). This interaction leads to acidification restricts uptake nutrients resulting competition symbiosis. At same time, neighboring during proliferation differentiation processes impacts immunity. article provides comprehensive overview crosstalk between cancer their microenvironment, deepening our understanding relevant findings pathways. contributes further regulation development evasion mechanisms while providing assistance advancing personalized therapies targeting pathways for anti-cancer treatment.

Язык: Английский

Процитировано

1
Harnessing CD8+ T cell dynamics in hepatitis B virus‐associated liver diseases: Insights, therapies and future directions DOI Creative Commons
Bing Yue, Yuxia Gao, Yi Hu

и другие.

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(7)

Опубликована: Июнь 27, 2024

Abstract Hepatitis B virus (HBV) infection playsa significant role in the etiology and progression of liver‐relatedpathologies, encompassing chronic hepatitis, fibrosis, cirrhosis, eventual hepatocellularcarcinoma (HCC). Notably, HBV stands as primary etiologicalfactor driving development HCC. Given contribution ofHBV to liver diseases, a comprehensive understanding immunedynamics microenvironment, spanning infection,fibrosis, HCC, is essential. In this review, we focused on thefunctional alterations CD8 + T cells within pathogenic livermicroenvironment from We thoroughly reviewed roles ofhypoxia, acidic pH, metabolic reprogramming, amino acid deficiency, inhibitory checkpointmolecules, immunosuppressive cytokines, gut‐liver communication shapingthe dysfunction microenvironment. Thesefactors significantly impact clinical prognosis. Furthermore, comprehensivelyreviewed cell‐based therapy strategies for diseases,encompassing infection, Strategies includeimmune checkpoint blockades, T‐cell targeting therapy, therapeuticT‐cell vaccination, adoptive transfer genetically engineered cells, along with combined usage programmed cell death protein‐1/programmeddeath ligand‐1 (PD‐1/PD‐L1) inhibitors mitochondria‐targeted antioxidants.Given that at various stages hepatitis Bvirus‐induced hepatocellular carcinoma (HBV HCC) shows promise, reviewedthe ongoing need research elucidate complex interplay between microenvironment toHCC. also discussed personalized treatment regimens, combining therapeuticstrategies harnessing gut microbiota modulation, which holds potential forenhanced benefits. conclusion, review delves into changes, during HCC progression, andrelated diseases.

Язык: Английский

Процитировано

7
Methionine restriction diets: Unravelling biological mechanisms and enhancing brain health DOI
Yi Liu,

Jingjing Guo,

Hao Cheng

и другие.

Trends in Food Science & Technology, Год журнала: 2024, Номер 149, С. 104532 - 104532

Опубликована: Май 14, 2024

Язык: Английский

Процитировано

5
Subcellular one carbon metabolism in cancer, aging and epigenetics DOI Creative Commons
Tiziano Bernasocchi, Raúl Mostoslavsky

Frontiers in Epigenetics and Epigenomics, Год журнала: 2024, Номер 2

Опубликована: Июль 31, 2024

The crosstalk between metabolism and epigenetics is an emerging field that gaining importance in different areas such as cancer aging, where changes significantly impacts the cellular epigenome, turn dictating chromatin adaptive mechanism to bring back metabolic homeostasis. A key pathway influencing organism's epigenetic state one-carbon (OCM), which includes folate methionine cycles. Together, these cycles generate S-adenosylmethionine (SAM), universal methyl donor essential for DNA histone methylation. SAM serves sole group methyltransferases, making it a crucial metabolite modifications. In this review, we will discuss how its byproduct, S-adenosylhomocysteine (SAH), along with enzymes cofactors involved OCM, may function compartments, particularly nucleus, directly regulate epigenome aging cancer.

Язык: Английский

Процитировано

5
Hydralazine Inhibits Cysteamine Dioxygenase to Treat Preeclampsia and Induce Senescence in Glioblastoma DOI Creative Commons
Kyosuke Shishikura, Jiasong Li, Yiming Chen

и другие.

Опубликована: Янв. 17, 2025

The vasodilator hydralazine (HYZ) has been used clinically for ∼ 70 years and remains on the World Health Organization’s List of Essential Medicines as a therapy preeclampsia. Despite its longstanding use concomitant progress toward general understanding vasodilation, target mechanism HYZ have remained unknown. We show that selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating metal cofactor alkylating one ligands. This covalent inactivation slows entry proteins into Cys/N-degron pathway ADO initiates. HYZ’s capacity to stabilize regulators G-protein signaling (RGS4/5) normally marked degradation explains effect blood vessel tension comports with prior associations insufficient RGS levels human preeclampsia analogous symptoms in mice. established importance glioblastoma led us test these cell types. Indeed, single treatment induced senescence, suggesting potential new HYZ-based this deadly brain cancer.

Язык: Английский

Процитировано

0
PLK3 weakens antioxidant defense and inhibits proliferation of porcine Leydig cells under oxidative stress DOI Creative Commons
Chujie Chen, Jinyan He, Weixian Huang

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 21, 2025

Aging is characterized by cellular degeneration and impaired physiological functions, leading to a decline in male sexual desire reproductive capacity. Oxidative stress (OS) lead testicular aging impairing the system, but potential mechanisms remain unclear. In present study, functional status of tissues from young aged boars was compared, transcriptional responses Leydig cells (LCs) hydrogen peroxide (H2O2)-induced senescence were explored, revealing role OS promoting system. 601 differentially expressed genes (DEGs) associated with OS, cell cycle regulation, intracellular processes identified. These DEGs significantly enriched critical pathways, including p53 signaling pathway, autophagy, senescence. Protein-protein interaction (PPI) network analysis unveiled 15 key related DNA replication, polo-like kinase 3 (PLK3) exhibiting increased expression under OS. vitro, PLK3 knockdown enhanced viability antioxidant capacity LCs This study deepens our understanding how respond provides new therapeutic targets for enhancing resistance oxidative damage tissue health.

Язык: Английский

Процитировано

0