Raman spectroscopy reveals oxidative stress-induced metabolic vulnerabilities in early-stage AR-negative prostate-cancer versus normal-prostate cell lines.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
03
04
2024
accepted:
14
08
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Quantitative Raman spectroscopy provides information-rich imaging of complex tissues. To illustrate its ability to characterise early-stage disease, we compared live P4E6, a low-grade Gleason-3 prostate-cancer cell line, to PNT2-C2, a normal prostate cell-line equivalent, thereby elucidating key molecular and mechanistic differences. Spectral changes from statistically relevant population sampling show P4E6 is defined by reduced DNA/RNA signatures (primarily base-pair modifications), increased protein-related signatures (synthesis), decreased whole-cell measured saturated and unsaturated fatty acids, and increased cholesterol and cholesterol ester (lipid storage). Signatures in the live-cell disease state point to the Warburg effect for aerobic glycolysis as the mechanism for cellular energy generation. A follow-on study involving catastrophic desiccation showed a key survival pathway in the cancer state in the structural robustness of DNA/RNA. Metabolic changes, namely in Warburg-to-oxidative-phosphorylation rerouting and reduced protein synthesis, were also shown. Such modifications limit cancer's resistance to oxidative damage, and thus its ability to utilise a higher redox homeostasis for metabolic advantage. The results demonstrate the ability of quantitative Raman spectroscopy to uncover, with full molecular-heterogeneity capture, mechanistic vulnerabilities in lowest-grade tumorigenic prostate cancer, thereby revealing underlying targets for disease disruption at early stage.
Identifiants
pubmed: 39455589
doi: 10.1038/s41598-024-70338-1
pii: 10.1038/s41598-024-70338-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25388Subventions
Organisme : Prostate Cancer UK
ID : RIA15- ST2-022
Pays : United Kingdom
Organisme : Aspen Center for Physics, National Science Foundation grant
ID : PHY-2210452
Informations de copyright
© 2024. The Author(s).
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