Hyper-energy metabolism of Oxidative phosphorylation and enhanced glycolysis contributes to radioresistance in glioma cells DOI

Yogesh Rai,

Ankit Tiwari, Rakesh Pandey

et al.

Free Radical Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 14

Published: Jan. 20, 2025

PurposeThe concept of dual-state hyper-energy metabolism characterized by elevated glycolysis and OxPhos has gained considerable attention during tumor growth metastasis in different malignancies. However, it is largely unknown how such metabolic phenotypes influence the radiation response aggressive cancers. Therefore, present study aimed to investigate impact (increased OxPhos) on a human glioma cell line.MethodsModulation mitochondrial electron transport chain was carried out using 2,4-dinitrophenol (DNP). Metabolic characterization assessing glucose uptake, lactate production, mass, membrane potential, ATP production. The examined growth, clonogenic survival, death assays. Macromolecular oxidation assessed DNA damage, lipid peroxidation, protein carbonylation assay.ResultsHypermetabolic OPM-BMG cells exhibited significant increase following irradiation as compared parental BMG-1 cells. Enhanced radioresistance evidenced α/β ratio (9.58) D1 dose (4.18 Gy) 4.36 2.19 Gy respectively. Moreover, were found exhibit increased resistance against radiation-induced death, macromolecular Inhibition complex-II significantly enhanced radiosensitivity cells.ConclusionOur results demonstrate that confer radioresistance. Consequently targeting combination with may overcome therapeutic cancers like glioma.

Language: Английский

Altered metabolism in cancer: insights into energy pathways and therapeutic targets DOI Creative Commons
Muhammad Tufail, Canhua Jiang, Ning Li

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 18, 2024

Language: Английский

Citations

75
The Warburg effect: a score for many instruments in the concert of cancer and cancer niche cells DOI Creative Commons

Martyna Jaworska,

Julia Szczudło,

Adrian Pietrzyk

et al.

Pharmacological Reports, Journal Year: 2023, Volume and Issue: 75(4), P. 876 - 890

Published: June 19, 2023

Abstract Although Warburg's discovery of intensive glucose uptake by tumors, followed lactate fermentation in oxygen presence was made a century ago, it is still an area intense research and development new hypotheses that, layer layer, unravel the complexities neoplastic transformation. This seemingly simple metabolic reprogramming cancer cells reveals intriguing, multi-faceted nature that may link various phenomena including cell signaling, proliferation, ROS generation, energy supply, macromolecules synthesis/biosynthetic precursor immunosuppression, or cooperation cancerous with cancer-associated fibroblasts (CAFs), known as reversed Warburg effect. According to current perception causes consequences effect, PI3K/Akt/mTOR are main signaling pathways concert transcription factors HIF-1, p53, c-Myc, modulate activity/expression key regulatory enzymes, PKM2, PDK1 tune most optimal setting for cell. turn secures adequate levels biosynthetic precursors, NADPH, NAD + , rapid ATP production meet increased demands intensively proliferating tumor cells. The end-product “aerobic glycolysis”, lactate, oncometabolite, provide fuel neighboring cells, facilitate metastasis immunosuppression together enabling progression. importance possible applicability presented issue best illustrated numerous trials agents targeting constituting promising strategy future anti-cancer regimens. In this review, we present aspects multifactorial phenomenon, depicting mechanisms benefits behind also pointing selected field anticancer therapy.

Language: Английский

Citations

63
Cancer metabolism and carcinogenesis DOI Creative Commons
Jianqiang Yang, Chloe Shay, Nabil F. Saba

et al.

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 29, 2024

Abstract Metabolic reprogramming is an emerging hallmark of cancer cells, enabling them to meet increased nutrient and energy demands while withstanding the challenging microenvironment. Cancer cells can switch their metabolic pathways, allowing adapt different microenvironments therapeutic interventions. This refers heterogeneity, in which cell populations use pathways sustain survival proliferation impact response conventional therapies. Thus, targeting heterogeneity represents innovative avenue with potential overcome treatment resistance improve outcomes. review discusses patterns developmental stages, summarizes molecular mechanisms involved intricate interactions within metabolism, highlights clinical vulnerabilities as a promising regimen. We aim unravel complex characteristics develop personalized approaches address distinct traits, ultimately enhancing patient

Language: Английский

Citations

38
Single-cell RNA sequencing explored potential therapeutic targets by revealing the tumor microenvironment of neuroblastoma and its expression in cell death DOI Creative Commons
Lei Sun, Wenwen Shao, Zhiheng Lin

et al.

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 5, 2024

Language: Английский

Citations

27
The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy DOI Creative Commons
Dongming Li, Donghui Cao, Yuanlin Sun

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 29, 2024

Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence mortality, deprives countless patients of health even life. According to global cancer statistics, there were an estimated 19.3 million new cases nearly 10 deaths in 2020, the age-standardized mortality rates 201.0 100.7 per 100,000, respectively. Although remarkable advancements have been made therapeutic strategies recently, overall prognosis remains optimistic. Consequently, are still many severe challenges be faced difficult problems solved therapy today. Epigallocatechin gallate (EGCG), natural polyphenol extracted from tea leaves, received much attention for antitumor effects. Accumulating investigations confirmed EGCG can inhibit tumorigenesis progression by triggering apoptosis, suppressing proliferation, invasion, migration, altering tumor epigenetic modification, overcoming chemotherapy resistance. Nevertheless, regulatory roles biomolecular mechanisms immune microenvironment, metabolic immunotherapy remain obscure. In this article, we summarized most recent updates about effects on microenvironment (TME), reprogramming, anti-cancer immunotherapy. The results demonstrated promote response cytotoxic lymphocytes dendritic cells (DCs), attenuate immunosuppression myeloid-derived suppressor (MDSCs) T (Tregs), tumor-promoting functions tumor-associated macrophages (TAMs), neutrophils (TANs), various stromal including cancer-associated fibroblasts (CAFs), endothelial (ECs), stellate cells, mesenchymal stem/stromal (MSCs). Additionally, suppress multiple reprogramming pathways, glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, nucleotide synthesis. Finally, EGCG, as immunomodulator checkpoint blockade, enhance immunotherapeutic efficacy may promising candidate conclusion, plays versatile TME which provides novel insights combined

Language: Английский

Citations

19
Hypoxia-Induced Reactive Oxygen Species: Their Role in Cancer Resistance and Emerging Therapies to Overcome It DOI Creative Commons
Eleicy Nathaly Mendoza, Maria Rosa Ciriolo, Fabio Ciccarone

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 94 - 94

Published: Jan. 15, 2025

Normal tissues typically maintain partial oxygen pressure within a range of 3–10% oxygen, ensuring homeostasis through well-regulated supply and responsive vascular network. However, in solid tumors, rapid growth often outpaces angiogenesis, creating hypoxic microenvironment that fosters tumor progression, altered metabolism resistance to therapy. Hypoxic regions experience uneven distribution with severe hypoxia the core due poor vascularization high metabolic consumption. Cancer cells adapt these conditions shifts, predominantly relying on glycolysis, by upregulating antioxidant defenses mitigate reactive species (ROS)-induced oxidative damage. Hypoxia-induced ROS, resulting from mitochondrial dysfunction enzyme activation, exacerbates genomic instability, aggressiveness, therapy resistance. Overcoming hypoxia-induced ROS cancer requires multifaceted approach targets various aspects biology. Emerging therapeutic strategies target resistance, focusing hypoxia-inducible factors, levels, subpopulations. Combining innovative therapies existing treatments holds promise for improving outcomes overcoming mechanisms.

Language: Английский

Citations

4
IGF2BP1/AIFM2 axis regulates ferroptosis and glycolysis to drive hepatocellular carcinoma progression DOI
Wei Peng, Jie Liang,

Xuanlv Qian

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111660 - 111660

Published: Feb. 1, 2025

Language: Английский

Citations

3
X‐Ray‐Triggered CO‐Release from Gold Nanocluster: All‐in‐One Nanoplatforms for Cancer Targeted Gas and Radio Synergistic Therapy DOI

Lei Cao,

Yating Yang, Yanlin Zheng

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(25)

Published: April 4, 2024

Glycolysis-dominant metabolic pathway in cancer cells can promote their therapeutic resistance against radiotherapy (RT). Carbon monoxide (CO) as a glycolysis inhibitor enhance the efficiency of RT. Herein, an X-ray responsive CO-releasing nanocomposite (HA@AuNC@CO) based on strong host-guest interactions between radiosensitizer and CO donor for enhanced RT is developed. The encapsulated gold nanoclusters (CD-AuNCs) effectively generate cytotoxic reactive oxygen species (ROS) under radiation, which not only directly inactivate but also induce situ gas generation from adamantane modified metal carbonyl (Ada-CO) inhibition. Both vitro vivo results demonstrate that HA@AuNC@CO exhibits active targeting toward CD44 overexpressed cells, along with excellent inhibition efficient cancer. This study offers new strategy combination therapy tumor treatment.

Language: Английский

Citations

17
Targeting tumor-intrinsic SLC16A3 to enhance anti-PD-1 efficacy via tumor immune microenvironment reprogramming DOI Creative Commons
Ting Yu, Zhaoyun Liu,

Qingxu Tao

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 589, P. 216824 - 216824

Published: March 23, 2024

Immunotherapy, especially immune checkpoint inhibitors, has revolutionized clinical practice within the last decade. However, primary and secondary resistance to immunotherapy is common in patients with diverse types of cancer. It well-acknowledged that tumor cells can facilitate formation immunosuppressive microenvironments via metabolism reprogramming, lactic acid, metabolite glycolysis, a significant contributor. SLC16A3 (also named as MCT4) transporter mediating acid efflux. In this study, we investigated role glycolysis aimed improve effects Slc16a3 inhibition. Bioinformatical analysis revealed expression glycolysis-related genes correlated less CD8

Language: Английский

Citations

16
Spautin-1 promotes PINK1-PRKN-dependent mitophagy and improves associative learning capability in an alzheimer disease animal model DOI Creative Commons
Juan Yi, Heling Wang, Guang Lu

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(12), P. 2655 - 2676

Published: July 25, 2024

Spautin-1 is a well-known macroautophagy/autophagy inhibitor via suppressing the deubiquitinases USP10 and USP13 promoting degradation of PIK3C3/VPS34-BECN1 complex, while its effect on selective autophagy remains poorly understood. Mitophagy form for removal damaged superfluous mitochondria autophagy-lysosome pathway. Here, we report surprising discovery that, spautin-1 as an effective inhibitor, it promotes PINK1-PRKN-dependent mitophagy induced by mitochondrial damage agents. Mechanistically, facilitates stabilization activation full-length PINK1 at outer membrane (OMM) binding to components TOMM complex (TOMM70 TOMM20), leading disruption import prevention PARL-mediated cleavage. Moreover, induces neuronal in

Language: Английский

Citations

12