Role of LDH in tumor glycolysis: Regulation of LDHA by small molecules for cancer therapeutics

Seminars in Cancer Biology, Год журнала: 2022, Номер 87, С. 184 - 195

Опубликована: Ноя. 9, 2022

Язык: Английский

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Metabolic reprogramming in cancer: Mechanisms and therapeutics

MedComm, Год журнала: 2023, Номер 4(2)

Опубликована: Март 27, 2023

Abstract Cancer cells characterized by uncontrolled growth and proliferation require altered metabolic processes to maintain this characteristic. Metabolic reprogramming is a process mediated various factors, including oncogenes, tumor suppressor genes, changes in tumor–host cell interactions, which help meet the needs of cancer anabolism promote development. dynamically variable, depending on type microenvironment, involves multiple pathways. These pathways have complex mechanisms involve coordination signaling molecules, proteins, enzymes, increases resistance traditional antitumor therapies. With development therapies, has been recognized as new therapeutic target for cells. Therefore, understanding how change can provide reference therapies treatment. Here, we systemically reviewed their alteration together with current regulation treatments other possible that are still under investigation. Continuous efforts needed further explore mechanism metabolism corresponding treatments.

Язык: Английский

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Impairing Tumor Metabolic Plasticity via a Stable Metal‐Phenolic‐Based Polymeric Nanomedicine to Suppress Colorectal Cancer

Advanced Materials, Год журнала: 2023, Номер 35(23)

Опубликована: Март 14, 2023

Targeting metabolic vulnerability of tumor cells is a promising anticancer strategy. However, the therapeutic efficacy existing metabolism-regulating agents often compromised due to tolerance resulting from plasticity, as well their poor bioavailability and tumor-targetability. Inspired by inhibitive effect N-ethylmaleimide on mitochondrial function, dendronized-polymer-functionalized metal-phenolic nanomedicine (pOEG-b-D-SH@NP) encapsulating maleimide-modified doxorubicin (Mal-DOX) developed enable improvement in overall delivery efficiency inhibition metabolism via multiple pathways. It observed that Mal-DOX its derived induces energy depletion CT26 colorectal cancer more efficiently than doxorubicin, shifts balance programmed cell death apoptosis toward necroptosis. Notably, pOEG-b-D-SH@NP simultaneously inhibits cellular oxidative phosphorylation glycolysis, thus potently suppressing growth peritoneal intestinal metastasis mouse models. Overall, study provides dendronized-polymer-derived nanoplatform for treatment cancers through impairing plasticity.

Язык: Английский

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Therapeutic application of natural products: NAD+ metabolism as potential target

Phytomedicine, Год журнала: 2023, Номер 114, С. 154768 - 154768

Опубликована: Март 13, 2023

Язык: Английский

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SIRT1 activated by AROS sensitizes glioma cells to ferroptosis via induction of NAD+ depletion-dependent activation of ATF3

Redox Biology, Год журнала: 2024, Номер 69, С. 103030 - 103030

Опубликована: Янв. 3, 2024

Ferroptosis is a type of programmed cell death resulting from iron overload-dependent lipid peroxidation, and could be promoted by activating transcription factor 3 (ATF3). SIRT1 an enzyme accounting for removing acetylated lysine residues target proteins consuming NAD+, but its role remains elusive in ferroptosis ATF3. In this study, we found was activated during the process RSL3-induced glioma ferroptosis. Moreover, aggravated activator SRT2183, suppressed SIRT inhibitor EX527 or when silenced with siRNA. These indicated sensitized cells to Furthermore, expressional upregulation nuclear translocation Silence ATF3 siRNA attenuated increases ferrous downregulation SLC7A11 GPX4 depletion cysteine GSH. Thus, inducting activation. Mechanistically, activation reinforced decline NAD+ FK866 that inhibit NAD + synthesis via salvage pathway, intracellular maintained at higher level supplement exogenous NAD+. Notably, caused RSL3 enhanced further inhibited EX527. consumption Finally, inducing reactive oxygen species-dependent AROS. Together, our study revealed AROS sensitizes ATF3-dependent inhibition GPX4.

Язык: Английский

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Lipid droplets provide metabolic flexibility for cancer progression

FEBS Letters, Год журнала: 2024, Номер 598(10), С. 1301 - 1327

Опубликована: Фев. 7, 2024

A hallmark of cancer cells is their remarkable ability to efficiently adapt favorable and hostile environments. Due a unique metabolic flexibility, tumor can grow even in the absence extracellular nutrients or stressful scenarios. To achieve this, need large amounts lipids build membranes, synthesize lipid‐derived molecules, generate energy other nutrients. Tumor potentiate strategies obtain from cells, pathways new lipids, mechanisms for efficient storage, mobilization, utilization these lipids. Lipid droplets (LDs) are organelles that collect supply eukaryotes it increasingly recognized accumulation LDs cells. Furthermore, an active role LD proteins processes underlying tumorigenesis has been proposed. Here, by focusing on three major classes LD‐resident (perilipins, lipases, acyl‐CoA synthetases), we provide overview contribution progression discuss during proliferation, invasion, metastasis, apoptosis, stemness

Язык: Английский

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NAMPT‐Driven M2 Polarization of Tumor‐Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer

Advanced Science, Год журнала: 2024, Номер 11(14)

Опубликована: Фев. 2, 2024

Abstract Nicotinamide phosphoribosyltransferase (NAMPT) is a metabolic enzyme with key roles in inflammation. Previous studies have examined the consequences of its upregulated expression cancer cells themselves, but are limited respect to role other within tumor microenvironment (TME) during colorectal (CRC) progression. Using single‐cell RNA sequencing (scRNA‐seq) data, it founded that NAMPT highly expressed SPP1 + tumor‐associated macrophages (TAMs), unique subset TAMs associated immunosuppressive activity. A high gene signature correlated worse prognostic outcomes CRC patients. The effect Nampt deletion myeloid compartment mice development explored. deficiency resulted HIF‐1α destabilization, leading reduction M2‐like TAM polarization. caused significant decreases efferocytosis activity macrophages, which enhanced STING signaling and induction type I IFN‐response genes. Expression these genes contributed anti‐tumoral immunity via potentiation cytotoxic T cell TME. Overall, findings suggest NAMPT‐initiated TAM‐specific can be useful predicting poor patient outcomes; strategies aimed at targeting may provide promising therapeutic approach for building an immunostimulatory TME

Язык: Английский

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Lutetium texaphyrin: A photocatalyst that triggers pyroptosis via biomolecular photoredox catalysis

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(9)

Опубликована: Фев. 21, 2024

Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of operation. Here, we report that biomolecular photoredox catalysis in cells might be an important mechanism underlying PhotoPyro. Our findings reveal the photocatalyst lutetium texaphyrin (

Язык: Английский

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Energy metabolism in health and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 18, 2025

Язык: Английский

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In defence of ferroptosis

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 2, 2025

Abstract Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained cellular defences. Ferroptosis increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation conceived to occur not an endogenous executioner, but withdrawal guardians that otherwise constantly oppose induction. Here, we profile key ferroptotic defence strategies including regulation, modulation enzymes metabolite systems: glutathione reductase (GR), suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase (NQO1), Dihydrofolate (DHFR), retinal reductases dehydrogenases (RDH) thioredoxin (TR). A common thread uniting all metabolites combat lipid during dependence on reductant, nicotinamide adenine dinucleotide phosphate (NADPH). We will outline how cells control central carbon metabolism produce NADPH necessary precursors defend against ferroptosis. Subsequently discuss evidence for dysregulation different disease contexts glucose-6-phosphate dehydrogenase deficiency, cancer neurodegeneration. Finally, several anti-ferroptosis therapeutic spanning use radical trapping agents, dependent redox support highlight current landscape clinical trials focusing

Язык: Английский

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