Summary of Study ST002585

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001665. The data can be accessed directly via it's Project DOI: 10.21228/M8GQ6R This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002585
Study TitleZinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo
Study SummaryUsing gas chromatography time-of-flight mass spectrometry GC-TOF MS (3), we performed untargeted metabolomic profiling on esophageal mucosa of Zn-treated vs Zn-untreated rats (n = 10 rats per cohort). Thirty-eight significantly altered metabolites (24 down-, 14 up-regulated, P < 0.05) were identified in the Zn-treated vs Zn-untreated esophagus. Of the 24 down-regulated metabolites, 15 (63%) were involved in anabolic/biosynthetic pathways, including amino acid/pyrimidine/purine metabolism and polyamine biosynthesis. Putrescine (intermediate in polyamine biosynthesis), shown to be up 6.4-fold in ESCC-bearing ZD esophagus (3), was down-regulated -3.96-fold in Zn-treated esophagus. Ornithine decarboxylase (ODC) is the rate liming enzyme in the polyamine biosynthetic pathway to form putrescine, which is converted into spermidine and spermine. Polyamines are indispensable for cell proliferation/tumor growth, and depletion of polyamines inhibits tumor growth (6). Of the 14 metabolites that were significantly up-regulated in the Zn-treated esophagus, five (37%) were carbohydrates, including glucose, which is up-regulated 3.4-fold, pointing to a decreased uptake of glucose and a reversal of the Warburg effect after Zn treatment. Critical to cancer aerobic glycolysis is the metabolic enzyme hexokinase 2 (HK2) that catalyzes the first committed step in glucose metabolism where glucose is phosphorylated to form glucose-6-phosphate. HK2 overexpression accounts for the high glycolytic rate in cancer cells (7). In summary, Zn treatment that significantly reduced ESCC incidence reversed classic cancer cell metabolic phenotypes such as increased glycolysis and nucleoside intermediates, with decrease in putrescine, increase in glucose, accompanied by down-regulation of metabolite enzymes ODC and HK2.
Institute
West Coast Metabolomics Center
Last NamePedrosa
First NameDiego
Address451 Health Science Dr, Davis, CA, 95616, USA
Emaildpedrosa@ucdavis.edu
Phone(530) 752-8129
Submit Date2023-04-20
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailGC-MS
Release Date2023-05-15
Release Version1
Diego Pedrosa Diego Pedrosa
https://dx.doi.org/10.21228/M8GQ6R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN004257
Analysis type MS
Chromatography type GC
Chromatography system Leco Pegasus IV GC
Column Restek Rtx-5Sil MS (30m x 0.25mm, 0.25um)
MS Type EI
MS instrument type GC-TOF
MS instrument name Leco Pegasus HT TOF
Ion Mode POSITIVE
Units normalized peak heights

MS:

MS ID:MS004004
Analysis ID:AN004257
Instrument Name:Leco Pegasus HT TOF
Instrument Type:GC-TOF
MS Type:EI
MS Comments:Acquisition of masses between 85-500 Scan rate 17 spec/sec Processing with in house software
Ion Mode:POSITIVE
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