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.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
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

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001665
Project DOI:doi: 10.21228/M8GQ6R
Project Title:Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo
Project Summary:We previously showed that replenishing Zn in Zn-deficient rats and supplementing Zn in Zn-sufficient rats inhibit the development of esophageal squamous cell carcinoma (ESCC) (1) and tongue squamous cell carcinoma (2). To determine if Zn has anticancer activity in established ESCC, we performed a 33-day Zn treatment study in 31 ESCC-bearing ZD male rats with 85% ESCC incidence (designated Zn-untreated) that were generated in a 20-wk Zn deficiency-promoted, N-nitrosomethylbenzylamine (NMBA)-induced ESCC experiment (3). The ESCC-bearing Zn-untreated male rats demonstrated oncogenic miR-31 and -21 upregulation (3, 4) and human ESCC-associated metabolic changes (3), with decreased levels of glycolytic intermediates and increased levels of anabolic/biosynthetic intermediates, changes pointing to a classic cancer cell remodeling of energy and nucleoside metabolism (5). The 31 ESCC-bearing Zn-untreated rats were randomized into two groups, viz Zn-untreated (n = 10) and Zn-treated (n = 21). While Zn-untreated rats continued on ZD diet and deionized water, Zn-treated rats were given deionized water supplemented with 25 ppm Zn as Zn gluconate (2) and paired-fed a ZS diet to Zn-untreated rats. This study was concluded after 33 days of Zn medication. We found that Zn therapy reduced ESCC incidence from 90 to 43%, a drop of 47%. We then determined if Zn intervention, that reduced ESCC incidence, would induce metabolic changes to reverse the ESCC-associated metabolome (3).
Institute:West Coast Metabolomics Center
Last Name:Pedrosa
First Name:Diego
Address:451 Health Science Dr, Davis, CA, 95616, USA
Email:dpedrosa@ucdavis.edu
Phone:(530) 752-8129

Subject:

Subject ID:SU002687
Subject Type:Mammal
Subject Species:Rattus norvegicus
Taxonomy ID:10116

Factors:

Subject type: Mammal; Subject species: Rattus norvegicus (Factor headings shown in green)

mb_sample_id local_sample_id treatment
SA259171Pool 1Pools
SA259172Pool 2Pools
SA259183A5_005Turmor bearing-untreated
SA259184A4_004Turmor bearing-untreated
SA259185A2_002Turmor bearing-untreated
SA259186A6_006Turmor bearing-untreated
SA259187A3_003Turmor bearing-untreated
SA259188A7_007Turmor bearing-untreated
SA259189A10_010Turmor bearing-untreated
SA259190A9_009Turmor bearing-untreated
SA259191A8_008Turmor bearing-untreated
SA259192A1_001Turmor bearing-untreated
SA259173A16_016Turmor bearing-Zn treated
SA259174A15_015Turmor bearing-Zn treated
SA259175A14_014Turmor bearing-Zn treated
SA259176A17_017Turmor bearing-Zn treated
SA259177A19_019Turmor bearing-Zn treated
SA259178A20_020Turmor bearing-Zn treated
SA259179A13_013Turmor bearing-Zn treated
SA259180A18_018Turmor bearing-Zn treated
SA259181A12_012Turmor bearing-Zn treated
SA259182A11_011Turmor bearing-Zn treated
Showing results 1 to 22 of 22

Collection:

Collection ID:CO002680
Collection Summary:At sacrifice, esophagi from Zn-treated vs Zn-untreated rats were isolated (n = 10 rats per cohort). Esophageal epithelium was prepared by using a blade to remove the submucosal and muscularis layers, snap-frozen in liquid nitrogen, and stored at –80 °C. Frozen esophageal samples from Zn-untreated and Zn-treated rats (20 mg per esophagus) were shipped on dry ice to the NIH West Coast Metabolomics Center, University of California, Davis.
Sample Type:Epithelial cells

Treatment:

Treatment ID:TR002699
Treatment Summary:Two treatments, 10 rats per treatment group Untreated group was given drinking water Zn-treated group was given Zn-gluconate in the drinking water.

Sample Preparation:

Sampleprep ID:SP002693
Sampleprep Summary:SOP_blood-GCMS-06052020.pdf

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

Chromatography:

Chromatography ID:CH003163
Instrument Name:Leco Pegasus IV GC
Column Name:Restek Rtx-5Sil MS (30m x 0.25mm, 0.25um)
Column Temperature:50 - 300
Flow Gradient:1 ml/min
Flow Rate:1 ml/min
Solvent A:Helium
Solvent B:Helium
Chromatography Type:GC

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
  logo