Mandatory role of endoplasmic reticulum in preserving NADPH regeneration in starved MDA-MB-231 breast cancer cells DOI Creative Commons
Sonia Carta, Vanessa Cossu,

Francesca Vitale

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(19), P. e38718 - e38718

Published: Sept. 28, 2024

Language: Английский

Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer DOI Creative Commons
Shan Liu,

Xingda Zhang,

Wenzheng Wang

et al.

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

Published: Nov. 21, 2024

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth contributes treatment resistance. In primary breast metabolic shifts such as the Warburg effect enhanced lipid synthesis are closely linked chemotherapy failure. Similarly, metastatic lesions often display distinct profiles that not only sustain but also confer resistance targeted therapies immunotherapies. The review emphasizes two major aspects: mechanisms driving in both how unique environments sites further complicate treatment. By targeting vulnerabilities at stages, new strategies could improve efficacy existing provide better outcomes for cancer patients.

Language: Английский

Citations

20

Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation DOI Creative Commons
A. Morelli, Felix Scholkmann

Biochimie, Journal Year: 2024, Volume and Issue: 221, P. 99 - 109

Published: Feb. 1, 2024

The process of cellular respiration occurs for energy production through catabolic reactions, generally with glucose as the first step. In present work, we introduce a novel concept understanding this process, based on our conclusion that metabolism is coupled to pentose phosphate pathway (PPP) and extra-mitochondrial oxidative phosphorylation in closed-loop process. According current standard model glycolysis, converted 6-phosphate (glucose 6-P) then fructose 6-phosphate, glyceraldehyde 3-phosphate pyruvate, which enters Krebs cycle mitochondria. However, it more likely pyruvate will be lactate. PPP, 6-P branched off from glycolysis used produce NADPH ribulose 5-phosphate (ribulose 5-P). Ribulose 5-P can 3-P. view, circular take place produced by PPP retrogradely 6-P. This repeated several times until complete degradation role mitochondria degrade lipids beta-oxidation acetyl-CoA; function producing ATP appears only secondary. proposed new bioenergetics allows resolution some previously unresolved controversies related provides deeper metabolic processes cell, including insights into Warburg effect.

Language: Английский

Citations

13

Unveiling the growing significance of metabolism in modulating immune cell function: exploring mechanisms and implications; a review DOI Open Access
Nicholas Aderinto, Muili Abdulbasit, Tangmi Djabo Eric Adrien

et al.

Annals of Medicine and Surgery, Journal Year: 2023, Volume and Issue: 85(11), P. 5511 - 5522

Published: Sept. 13, 2023

Immunometabolism has emerged as a rapidly growing field of research, holding significant promise for personalised medicine and precision immunotherapy. This review explores the intricate relationship between immune function metabolic processes, emphasising their profound impact on various immune-related disorders. Understanding how dysregulation contributes to pathogenesis these disorders remains critical research gap. Therefore, this aims bridge that gap by examining key pathways involved specific implications in cell function. Key pathways, including glycolysis, mitochondrial metabolism, fatty acid amino are discussed context Dysregulation can disrupt activation, differentiation, overall function, contributing disease pathogenesis. alterations' molecular mechanisms is essential developing targeted therapeutic interventions. The also emphasises importance unique profiles individuals influence treatment outcomes, highlighting need tailored approaches. Integrating profiling into clinical practice enhance efficacy improve patient outcomes. Investigating significance immunometabolism diverse contexts will facilitate translation findings practice. Moreover, refining strategies based individual contribute advancing

Language: Английский

Citations

13

Advancements in Analyzing Tumor Metabolites through Chemical Derivatization-Based Chromatography DOI

Ye Lu,

Huamin Zhang,

Bing-Jun Zhou

et al.

Journal of Chromatography A, Journal Year: 2023, Volume and Issue: 1706, P. 464236 - 464236

Published: July 22, 2023

Language: Английский

Citations

6

A fingerprint of 2-[18F]FDG radiometabolites – How tissue-specific metabolism beyond 2-[18F]FDG-6-P could affect tracer accumulation DOI Creative Commons

Eva‐Maria Patronas,

Theresa Balber, Anne Miller

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(11), P. 108137 - 108137

Published: Oct. 6, 2023

Studies indicate that the radiotracer 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) can be metabolized beyond 2-[18F]FDG-6-phosphate (2-[18F]FDG-6-P), but its metabolism is incompletely understood. Most importantly, it remains unclear whether downstream affects tracer accumulation in vivo. Here we present a fingerprint of 2-[18F]FDG radiometabolites over time cancer cells, corresponding tumor xenografts and murine organs. Strikingly, representing glycogen or oxPPP correlated inversely with across all examined tissues. Recent studies suggest not only hexokinase, also hexose-6-phosphate dehydrogenase (H6PD), an enzyme oxidative pentose phosphate pathway (oxPPP), determines accumulation. However, little known about glucose-6-phosphate (G6PD). Our mechanistic vitro experiments on role propose via both G6PD H6PD, data from separate knockdown diverging roles metabolism. Overall, tissue-specific 2-[18F]FDG-6-P could matter for imaging.

Language: Английский

Citations

2

Unexpected chronic lymphocytic leukemia B cell activation by bisphosphonates DOI Creative Commons
Andrea Nicola Mazzarello,

Elena Gugiatti,

Vanessa Cossu

et al.

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 73(2)

Published: Jan. 27, 2024

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, often presenting comorbidities like osteoporosis and requiring, in relevant proportion cases, treatment with bisphosphonates (BPs). This class drugs was shown preclinical investigations to also possess anticancer properties. We started an vitro study effects BPs on CLL B cells activated by microenvironment-mimicking stimuli observed that, depending drug concentration, hormetic were induced leukemic cells. Higher doses cytotoxicity whereas at lower concentrations, more likely occurring vivo, generated protective effect from spontaneous chemotherapy-induced apoptosis, augmented cell activation/proliferation. CLL-activation promoted associated markers poor prognosis required presence bystander stromal Functional experiments suggested that this phenomenon involves release soluble factors increased cellular contact between stroma Since patients present such as considering diverse outcomes both progression response among patients, illustrating holds potential significance driving additional investigations.

Language: Английский

Citations

0

Exploiting the metabolic vulnerability of circulating tumour cells DOI
Munise Merteroglu, Massimo Santoro

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(6), P. 541 - 556

Published: April 4, 2024

Language: Английский

Citations

0

The pivotal role of endoplasmic reticulum in FDG uptake in cancer cells DOI Creative Commons

Francesca Vitale,

Maddalena Ghelardoni,

Sabrina Chiesa

et al.

EJNMMI Research, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 12, 2024

Language: Английский

Citations

0

The Glucose-Glutamine Metabolic Interplay in MCF-7 Cells, a Hormone-Sensitive Breast Cancer Model DOI Creative Commons
Sonia Carta,

Maddalena Ghelardoni,

Francesca Vitale

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(7)

Published: July 16, 2024

Background: Selective deprivation of glutamine has been shown to accelerate the generation reactive oxygen species (ROS) and impair activity a specific pentose phosphate pathway (PPP) located within endoplasmic reticulum (ER). The consequent oxidative damage suggests that glucose flux through this reticular might contribute redox stress breast cancer cells. We thus evaluated whether response is reproduced when shortage coupled with deprivation. Methods: Cancer growth, metabolic plasticity status were under saturating conditions after 48 h starvation (glucose 2.5 mM, 0.5 mM). Seahorse technology was used estimate adenosine triphosphate (ATP)-linked ATP-independent consumption rate (OCR) as well proton efflux (PER). 18F-fluoro-deoxy-glucose (FDG) uptake LigandTracer device. Proliferation estimated by carboxyfluorescein-diacetate-succinimidyl ester (CFSE) staining, while cell viability propidium iodide exclusion assay. Results: Starvation reduced proliferation MCF-7 cells without affecting their viability. It also decreased lactate release PER. Overall OCR left unchanged although ATP-synthase dependent fraction increased nutrient shortage. Glutaminolysis inhibition selectively impaired oligomycin-sensitive in control starved cultures, respectively. combined cytosolic mitochondrial markers stress. expression unfolded protein marker GRP78. By contrast, hexose-6P-dehydrogenase (H6PD) decreasing ER-PPP documented profound impairment FDG. Conclusions: When deprivation, does not elicit expected enhancement ROS studied line. Combined ER-PPP, observation interferes metabolism regulate balance.

Language: Английский

Citations

0

Mandatory role of endoplasmic reticulum in preserving NADPH regeneration in starved MDA-MB-231 breast cancer cells DOI Creative Commons
Sonia Carta, Vanessa Cossu,

Francesca Vitale

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(19), P. e38718 - e38718

Published: Sept. 28, 2024

Language: Английский

Citations

0