Molecular targets of spermidine: implications for cancer suppression.
autophagy
cancer
hypusination
immunosurveillance
molecular targets
spermidine
Journal
Cell stress
ISSN: 2523-0204
Titre abrégé: Cell Stress
Pays: Austria
ID NLM: 101718867
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
15
05
2023
revised:
14
06
2023
accepted:
21
06
2023
medline:
11
7
2023
pubmed:
11
7
2023
entrez:
11
7
2023
Statut:
epublish
Résumé
Spermidine is a ubiquitous, natural polyamine with geroprotective features. Supplementation of spermidine extends the lifespan of yeast, worms, flies, and mice, and dietary spermidine intake correlates with reduced human mortality. However, the crucial role of polyamines in cell proliferation has also implicated polyamine metabolism in neoplastic diseases, such as cancer. While depleting intracellular polyamine biosynthesis halts tumor growth in mouse models, lifelong external spermidine administration in mice does not increase cancer incidence. In contrast, a series of recent findings points to anti-neoplastic properties of spermidine administration in the context of immunotherapy. Various molecular mechanisms for the anti-aging and anti-cancer properties have been proposed, including the promotion of autophagy, enhanced translational control, and augmented mitochondrial function. For instance, spermidine allosterically activates mitochondrial trifunctional protein (MTP), a bipartite protein complex that mediates three of the four steps of mitochondrial fatty acid (β-oxidation. Through this action, spermidine supplementation is able to restore MTP-mediated mitochondrial respiratory capacity in naïve CD8
Identifiants
pubmed: 37431488
doi: 10.15698/cst2023.07.281
pii: CST0273E115
pmc: PMC10320397
doi:
Types de publication
Editorial
Langues
eng
Pagination
50-58Informations de copyright
Copyright: © 2023 Zimmermann et al.
Déclaration de conflit d'intérêts
Conflict of Interest: F.M. is a scientific cofounder of Samsara Therapeutics, a company that develops novel pharmacological autophagy inducers. F.M. has equity interests in and is advisor of The Longevity Labs (TLL). S.J.H. and A.Z. declare no conflict of interest.
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