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L-glyceraldehyde inhibits neuroblastoma cell growth via a multi-modal mechanism on metabolism and Signaling

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Item Type:Article
Title:L-glyceraldehyde inhibits neuroblastoma cell growth via a multi-modal mechanism on metabolism and Signaling
Creators Name:Forbes, M. and Kempa, R. and Mastrobuoni, G. and Rayman, L. and Pietzke, M. and Bayram, S. and Arlt, B. and Spruessel, A. and Deubzer, H.E. and Kempa, S.
Abstract:Glyceraldehyde (GA) is a three-carbon monosaccharide that can be present in cells as a by-product of fructose metabolism. Bruno Mendel and Otto Warburg showed that the application of GA to cancer cells inhibits glycolysis and their growth. However, the molecular mechanism by which this occurred was not clarified. We describe a novel multi-modal mechanism by which the L-isomer of GA (L-GA) inhibits neuroblastoma cell growth. L-GA induces significant changes in the metabolic profile, promotes oxidative stress and hinders nucleotide biosynthesis. GC-MS and (13)C-labeling was employed to measure the flow of carbon through glycolytic intermediates under L-GA treatment. It was found that L-GA is a potent inhibitor of glycolysis due to its proposed targeting of NAD(H)-dependent reactions. This results in growth inhibition, apoptosis and a redox crisis in neuroblastoma cells. It was confirmed that the redox mechanisms were modulated via L-GA by proteomic analysis. Analysis of nucleotide pools in L-GA-treated cells depicted a previously unreported observation, in which nucleotide biosynthesis is significantly inhibited. The inhibitory action of L-GA was partially relieved with the co-application of the antioxidant N-acetyl-cysteine. We present novel evidence for a simple sugar that inhibits cancer cell proliferation via dysregulating its fragile homeostatic environment.
Keywords:Cancer Metabolism, Redox Mechanisms, Nucleotide Biosynthesis, Glycolytic Inhibition, Animals, Mice
Source:Cancers
ISSN:2072-6694
Publisher:MDPI
Volume:16
Number:9
Page Range:1664
Date:May 2024
Official Publication:https://doi.org/10.3390/cancers16091664
PubMed:View item in PubMed

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