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Citrate is a key metabolite of the Krebs cycle that can also be exported in the cytosol, where it performs several functions. In normal cells, citrate sustains protein acetylation, lipid synthesis, gluconeogenesis, insulin secretion, bone tissues formation, spermatozoid mobility, and immune response. Dysregulation of citrate metabolism is implicated in several pathologies, including cancer. Here we discuss how cancer cells use citrate to sustain their proliferation, survival, and metastatic progression. Also, we propose two paradoxically opposite strategies to reduce tumour growth by targeting citrate metabolism in preclinical models. In the first strategy, we propose to administer in the tumor microenvironment a high amount of citrate, which can then act as a glycolysis inhibitor and apoptosis inducer, whereas the other strategy targets citrate transporters to starve cancer cells from citrate. These strategies, effective in several preclinical in vitro and in vivo cancer models, could be exploited in clinics, particularly to increase sensibility to current anti-cancer agents.
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http://dx.doi.org/10.1016/j.bbcan.2023.188987 | DOI Listing |
Front Chem
February 2025
Prevention and Treatment Center, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China.
Oxidative stress-induced damage is a significant contributor to the impairment of Leydig cells in the testes, potentially diminishing the secretion of testosterone and other androgens, thereby resulting in testosterone deficiency. Salidroside, the principal bioactive constituent derived from Rhodiola, exhibits potent antioxidant properties. This study aims to investigate the underlying mechanisms by which salidroside enhances testosterone secretion.
View Article and Find Full Text PDFHeliyon
February 2025
Special Centre for Molecular Medicine, Jawaharlal Nehru University, Delhi, India.
Microglia, the immune cells of the central nervous system (CNS), play key roles in neurogenesis, myelination, synaptic transmission, immune surveillance, and neuroinflammation. Inflammatory responses in microglia can lead to oxidative stress and neurodegeneration, contributing to diseases like Parkinson's and Alzheimer's. The enzyme glucose-6-phosphate dehydrogenase (G6PD) is essential for producing nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), which neutralizes oxidative stress.
View Article and Find Full Text PDFFoods
February 2025
State Key Laboratory of Food Science and Resources, Engineering Research Center for Biomass Conversion, Ministry of Education, Nanchang University, Nanchang 330047, China.
In the context of pollution-free waste treatment, anaerobic fermentation liquid (AFL), a prominent by-product of biogas engineering, has emerged as a focal point in contemporary research. Concurrently, vitamin C, an active compound abundant in fruits and vegetables, possesses extensive application potential. The development of efficient extraction processes and the utilization of its biological activities have garnered significant attention from researchers.
View Article and Find Full Text PDFInt J Mol Sci
February 2025
Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Dysregulated iron metabolism-induced ferroptosis is considered a key pathological mechanism in the development of osteoporosis (OP). G protein-coupled receptor 30 (GPR30, also known as Gper1) is an estrogen-binding receptor that has shown therapeutic benefits in patients with certain degenerative diseases. Moreover, several studies have demonstrated the anti-ferroptotic effects of estrogen receptor activation.
View Article and Find Full Text PDFAgeing Res Rev
March 2025
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. Electronic address:
A key molecule in cellular metabolism, citrate is essential for lipid biosynthesis, energy production, and epigenetic control. The etiology of Alzheimer's disease (AD), a progressive neurodegenerative illness marked by memory loss and cognitive decline, may be linked to dysregulated citrate transport, according to recent research. Citrate transporters, which help citrate flow both inside and outside of cells, are becoming more and more recognized as possible participants in the molecular processes underlying AD.
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