PXD048695-1

PXD048695 is an original dataset announced via ProteomeXchange.

Title	L-Glyceraldehyde inhibits neuroblastoma cell 1 growth via a multi-modal mechanism on metabolism 2 and signaling
Description	Glyceraldehyde (GA) is a 3-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. This phenomenon was extensively studied up until the 1970’s. 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 cancer cell growth. L-GA induces significant changes in the metabolic profile, promotes oxidative stress and hinders nucleotide biosynthesis. GC-MS and 13C-labelling 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 the cancer cell. It was confirmed that the redox mechanisms were modulated via L-GA by proteomic analysis. This elucidated a specific subset of proteins harbouring oxidoreductase and antioxidant activity. Analysis of nucleotide pools in L-GA treated cells depicted a remarkable and previously unreported phenotype. Nucleotide biosynthesis in neuroblastoma cells is significantly inhibited upon L-GA treatment. Through the application of the antioxidant N-acetyl-cysteine in conjunction with L-GA, metabolic inhibition was partially relieved. We present novel evidence for the multi-modal mechanism of L-GA action in neuroblastoma cells. Specifically, a simple sugar that inhibits the growth of cancer via dysregulating the fragile homeostatic environment inherent to the cancerous cell.
HostingRepository	PRIDE
AnnounceDate	2024-05-21
AnnouncementXML	Submission_2024-05-21_09:18:26.969.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guido Mastrobuoni
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-18 12:43:38	ID requested
⏵ 1	2024-05-21 09:18:27	announced

10.3390/cancers16091664;

Forbes M, Kempa R, Mastrobuoni G, Rayman L, Pietzke M, Bayram S, Arlt B, Spruessel A, Deubzer HE, Kempa S, L-Glyceraldehyde Inhibits Neuroblastoma Cell Growth via a Multi-Modal Mechanism on Metabolism and Signaling. Cancers (Basel), 16(9):(2024) [pubmed]

submitter keyword: metabolism, neuroblastoma,cancer, redox, glycolysis

Stefan Kempa
contact affiliation	Kempa Lab - Quantitative Proteomics and Metabolomics Berlin Institute for Medical Systems Biology (BIMSB) Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft Hannoversche Straße 28 10115 Berlin
contact email	stefan.kempa@mdc-berlin.de
lab head
Guido Mastrobuoni
contact affiliation	Berlin Institute for Medical Systems Biology at the Max Delbrueck Centrum for Molecular Medicine
contact email	guido.mastrobuoni@mdc-berlin.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD048695

PRIDE project URI

• PRIDE
  1. PXD048695
     1. Label: PRIDE project
     2. Name: L-Glyceraldehyde inhibits neuroblastoma cell 1 growth via a multi-modal mechanism on metabolism 2 and signaling