Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer DOI Open Access

Chi Yeon Hwang,

Wonchae Choe,

Kyung‐Sik Yoon

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(22), P. 4932 - 4932

Published: Nov. 21, 2022

The ketone bodies (KBs) β-hydroxybutyrate and acetoacetate are important alternative energy sources for glucose during nutrient deprivation. KBs synthesized by hepatic ketogenesis catabolized to acetyl-CoA through ketolysis in extrahepatic tissues, followed the tricarboxylic acid cycle electron transport chain ATP production. Ketogenesis regulated key rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA synthase 2 succinyl-CoA:3-oxoacid-CoA transferase, respectively. participate various cellular processes as signaling molecules. bind G protein-coupled receptors. most abundant KB, β-hydroxybutyrate, regulates gene expression other functions inducing post-translational modifications. protect tissues regulating inflammation oxidative stress. Recently, interest has been increasing due their potential treatment of diseases such neurological cardiovascular cancer. Cancer cells reprogram metabolism maintain rapid cell growth proliferation. Dysregulation KB also plays a role tumorigenesis types Targeting metabolic changes dietary interventions, including fasting ketogenic diets, shown beneficial effects cancer therapy. Here, we review current knowledge molecular mechanisms involved regulation functions, therapeutic diets

Language: Английский

The role of lipid metabolic reprogramming in tumor microenvironment DOI Creative Commons
Kai Yang, Xiaokun Wang, Chenghu Song

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(6), P. 1774 - 1808

Published: Jan. 1, 2023

Metabolic reprogramming is one of the most important hallmarks malignant tumors.Specifically, lipid metabolic has marked impacts on cancer progression and therapeutic response by remodeling tumor microenvironment (TME).In past few decades, immunotherapy revolutionized treatment landscape for advanced cancers.Lipid plays pivotal role in regulating immune to immunotherapy.Here, we systematically reviewed characteristics, mechanism, cells TME, appraised effects various cell death modes (specifically ferroptosis) metabolism, summarized antitumor therapies targeting metabolism.Overall, profound microenvironment; therefore, may lead development innovative clinical applications including sensitizing immunotherapy.

Language: Английский

Citations

69
Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential DOI Creative Commons

Yu-Ling Xiao,

Yue Gong,

Ying-Jia Qi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 11, 2024

Abstract Diet, serving as a vital source of nutrients, exerts profound influence on human health and disease progression. Recently, dietary interventions have emerged promising adjunctive treatment strategies not only for cancer but also neurodegenerative diseases, autoimmune cardiovascular metabolic disorders. These demonstrated substantial potential in modulating metabolism, trajectory, therapeutic responses. Metabolic reprogramming is hallmark malignant progression, deeper understanding this phenomenon tumors its effects immune regulation significant challenge that impedes eradication. Dietary intake, key environmental factor, can tumor metabolism. Emerging evidence indicates might affect the nutrient availability tumors, thereby increasing efficacy treatments. However, intricate interplay between pathogenesis other diseases complex. Despite encouraging results, mechanisms underlying diet-based remain largely unexplored, often resulting underutilization management. In review, we aim to illuminate various interventions, including calorie restriction, fasting-mimicking diet, ketogenic protein restriction high-salt high-fat high-fiber aforementioned diseases. We explore multifaceted impacts these encompassing their immunomodulatory effects, biological impacts, molecular mechanisms. This review offers valuable insights into application therapies

Language: Английский

Citations

66
Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets DOI Creative Commons
Shaosen Zhang,

Xinyi Xiao,

Yonglin Yi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Language: Английский

Citations

59
An Engineered Butyrate-Derived Polymer Nanoplatform as a Mucosa-Healing Enhancer Potentiates the Therapeutic Effect of Magnolol in Inflammatory Bowel Disease DOI
Fan Xi, Zhuangzhuang Zhang, Wenxia Gao

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 18(1), P. 229 - 244

Published: Dec. 19, 2023

Colonic epithelial damage and dysregulated immune response are crucial factors in the progression exacerbation of inflammatory bowel disease (IBD). Nanoenabled targeted drug delivery to inflamed intestinal mucosa has shown promise inducing maintaining colitis remission, while minimizing side effects. Inspired by excellent antioxidative anti-inflammatory efficacy naturally derived magnolol (Mag) gut homeostasis regulation microbiota-derived butyrate, we developed a pH/redox dual-responsive butyrate-rich polymer nanoparticle (PSBA) as an oral Mag system for combinational therapy IBD. PSBA showed high butyrate content 22% effectively encapsulated Mag. The Mag-loaded nanoparticles (PSBA@Mag) demonstrated colonic pH reduction-responsive release, ensuring efficient retention adhesion colon mice. PSBA@Mag not only normalized level reactive oxygen species effectors but also restored barrier function both ulcerative Crohn's mouse models. Importantly, promoted migration healing ability cells vitro vivo, sensitizing therapeutic animal Moreover, transcriptomics metabolism analyses revealed that mitigated inflammation suppressing production pro-inflammatory cytokines chemokines restoring lipid metabolism. Additionally, this nanomedicine modulated microbiota inhibiting pathogenic Proteus Escherichia-Shigella promoting proliferation beneficial probiotics, including Lachnoclostridium, Lachnospiraceae_NK4A136_group norank_f_Ruminococcaceae. Overall, our findings highlight potential butyrate-functionalized polymethacrylates versatile effective nanoplatforms repair combating IBD other gastrointestinal disorders.

Language: Английский

Citations

45
Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo DOI Creative Commons
L. Francisco Lorenzo‐Martín, Tania Hübscher, Amber D. Bowler

et al.

Nature, Journal Year: 2024, Volume and Issue: 629(8011), P. 450 - 457

Published: April 24, 2024

Three-dimensional organoid culture technologies have revolutionized cancer research by allowing for more realistic and scalable reproductions of both tumour microenvironmental structures

Language: Английский

Citations

41
Gut microbiota modulate CD8 + T cell immunity in gastric cancer through Butyrate/GPR109A/HOPX DOI Creative Commons
Xiang Yu,

Jinzhou Ou,

Lingzhi Wang

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 6, 2024

The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet role these factors on gastric cancer (GC) remains uncertain. In this work, analysis composition SCFA content in blood feces both healthy individuals GC patients indicated that significant reductions abundance intestinal bacteria involved production were observed compared with controls. ABX mice transplanted fecal from developed more tumors during induction had lower levels butyric acid. Supplementation butyrate along H. pylori N-methyl-N-nitrosourea (MNU) WT GPR109A−/−mice resulted fewer IFN-γ+ CD8+ T cells, but effect was significantly weakened after knockout GPR109A. Furthermore, vitro cells co-cultured or CAR-Claudin 18.2+ as well vivo tumor-bearing studies, have enhanced killing function against through G protein-coupled receptor 109A (GPR109A) homologous domain protein box (HOPX). Together, data highlighted restoration microbial cell cytotoxicity via GPR109A/HOPX, thus inhibiting carcinogenesis, which suggests a novel theoretical foundation for management GC.

Language: Английский

Citations

30
Emerging targets in lipid metabolism for cancer therapy DOI Creative Commons
Alexander R. Terry, Nissim Hay

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(6), P. 537 - 551

Published: May 17, 2024

Cancer cells perturb lipid metabolic pathways for a variety of pro-tumorigenic functions, and deregulated cellular metabolism is hallmark cancer cells. Although alterations in have been appreciated over 20 years, there are no FDA-approved treatments that target lipid-related pathways. Recent advances pertaining to cell fatty acid synthesis (FAS), desaturation, uptake, microenvironmental dietary lipids, tumor-infiltrating immune illuminated promising clinical applications targeting metabolism. This review highlights emerging targets tumor may soon impact treatment.

Language: Английский

Citations

21
Multi-stage mechanisms of tumor metastasis and therapeutic strategies DOI Creative Commons
Zaoqu Liu, Jingqi Chen, Yuqing Ren

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 11, 2024

The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases the disease and progress under intense evolutionary pressures. Organ-specific relies on formation pre-metastatic niche (PMN), with diverse cell types complex interactions contributing to this concept, adding a new dimension traditional cascade. Prior metastatic dissemination, as orchestrators PMN formation, primary tumor-derived extracellular vesicles prepare fertile microenvironment for settlement colonization circulating cells distant secondary sites, significantly impacting cancer progression outcomes. Obviously, solely intervening sites passively after macrometastasis is often insufficient. Early prediction holistic, macro-level control represent future directions therapy. This review emphasizes dynamic intricate systematic alterations that progresses, illustrates immunological landscape creation, deepens understanding treatment modalities pertinent metastasis, thereby identifying some prognostic predictive biomarkers favorable early predict occurrence design appropriate combinations.

Language: Английский

Citations

21
Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review DOI Creative Commons
Aleksandra Golonko, Tomasz Pienkowski, Renata Świsłocka

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 9, 2024

Abstract Immunotherapy is emerging as a promising avenue in oncology, gaining increasing importance and offering substantial advantages when compared to chemotherapy or radiotherapy. However, the context of immunotherapy, there potential for immune system either support hinder administered treatment. This review encompasses recent pivotal studies that assess influence dietary elements, including vitamins, fatty acids, nutrients, small molecules, patterns, caloric restriction, on ability modulate responses. Furthermore, article underscores how these factors have modify enhance effectiveness anticancer immunotherapy. It emphasizes necessity additional research comprehend underlying mechanisms optimizing efficacy therapy defining strategies may reduce cancer-related morbidity mortality. Persistent investigation this field holds significant promise improving cancer treatment outcomes maximizing benefits

Language: Английский

Citations

19
Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases DOI Creative Commons

Weiyi Yao,

Xinting Hu,

Xin Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 16, 2024

Abstract Histone post-translational modifications (HPTMs), as one of the core mechanisms epigenetic regulation, are garnering increasing attention due to their close association with onset and progression diseases potential targeted therapeutic agents. Advances in high-throughput molecular tools abundance bioinformatics data have led discovery novel HPTMs which similarly affect gene expression, metabolism, chromatin structure. Furthermore, a growing body research has demonstrated that histone also play crucial roles development various diseases, including cancers, cardiovascular infectious psychiatric disorders, reproductive system diseases. This review defines nine modifications: lactylation, citrullination, crotonylation, succinylation, SUMOylation, propionylation, butyrylation, 2-hydroxyisobutyrylation, 2-hydroxybutyrylation. It comprehensively introduces modification processes these HPTMs, transcription, replication, DNA repair recombination, structure, well involvement promoting occurrence clinical applications targets biomarkers. Moreover, this provides detailed overview HPTM inhibitors targeting emerging strategies treatment multiple while offering insights into future prospects challenges. Additionally, we briefly introduce techniques field research.

Language: Английский

Citations

18