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.
| Study ID | ST002585 |
| Study Title | Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo |
| Study Summary | Using 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 Name | Pedrosa |
| First Name | Diego |
| Address | 451 Health Science Dr, Davis, CA, 95616, USA |
| dpedrosa@ucdavis.edu | |
| Phone | (530) 752-8129 |
| Submit Date | 2023-04-20 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | cdf |
| Analysis Type Detail | GC-MS |
| Release Date | 2023-05-15 |
| Release Version | 1 |
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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 |
