Summary of Study ST003029

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 PR001882. The data can be accessed directly via it's Project DOI: 10.21228/M8FQ52 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 IDST003029
Study TitleEstrogen-mediated inhibition of purine metabolism and cell cycle arrest as a novel therapeutic approach in colorectal cancer cells
Study SummaryPurine metabolism is upregulated in various cancers including colorectal cancer (CRC). While previous research has elucidated the role of Estrogen (E2) in metabolism remodeling and ATP production, its effects on purine metabolism remained unexplored. This study investigates the impact of E2 signalling on purine metabolism in CRC cells. We demonstrate, for the first time, a protective effect of E2 on CRC cells by targeting the purine synthesis pathway through its receptor estrogen receptor α (ERα). A full metabolomic profiling, next generation sequencing (NGS) and integrated OMICS were conducted for HCT-116 cells treated with E2 with and without silencing ERα. Our results revealed an enrichment of the purine metabolic pathway, with 27 genes in the de novo purine synthesis pathway downregulated in E2-treated CRC cells. Besides, E2-induced DNA damage, cell cycle arrest, and apoptosis are ERα-dependent. Our findings suggest potential therapeutic avenues for CRC treatment through antimetabolites targeting purine synthesis, as E2 treatment reduces the expression of relevant metabolites.
Institute
Sharjah Institute for Medical Research
Last NameFacility
First NameCore
AddressM32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah, Sharjah, UAE, Sharjah, 000, United Arab Emirates
Emailtims-tof@sharjah.ac.ae
Phone+971 6 5057656
Submit Date2023-11-29
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2024-05-31
Release Version1
Core Facility Core Facility
https://dx.doi.org/10.21228/M8FQ52
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN004966
Analysis type MS
Chromatography type Reversed phase
Chromatography system Bruker Elute
Column Hamilton® Intensity Solo 2 C18 column (2.1 × 100 mm, 1.8 µm)
MS Type ESI
MS instrument type QTOF
MS instrument name Bruker timsTOF
Ion Mode POSITIVE
Units AU

MS:

MS ID:MS004706
Analysis ID:AN004966
Instrument Name:Bruker timsTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:The ESI source condition for every injection was as follows: The drying gas flow rate was 10.0 L/min at a temp of 220 ◦C; the capillary voltage was set at 4500 V; the End Plate offset was set at 500 V; the nebulizer pressure of 2.2 bar. The acquisition involved two segments; auto MS scan, which ranged from 0 to 0.3 min for the calibrant sodium formate, and auto MS/MS scan with CID acquisition, which included fragmentation and ranged from 0.3 to 30 min. The acquisition in both segments was performed using the positive mode at 12 Hz. The automatic in-run mass scan range was from 50 to 1300 m/z, the width of the precursor ion was ±0.5, the cycle time was 0.5 sec, and the threshold was 400 cts. Active exclusion was excluded after 3 spectra and released after 0.2 min. For MS2 acquisition the data dependent acquisition (DDA) was used, and the collision energy stepping fluctuated between 100 and 250% set at 20 eV. M/Z measurements were externally calibrated using 10 mM of sodium formate before sample analysis. In addition, sodium formate solution was injected at the beginning of each sample run and used for internal calibration during data processing TRX-2101/RT-28-calibrants for Bruker T-ReX LC-QTOF (Nova Medical Testing Inc.) was injected before sample analysis to check and test the performance of the column, reversed-phase liquid chromatography (RPLC) separation, multipoint retention time calibration, and the mass spectrometer. Also, TRX-3112-R/MS Certified Human serum for Bruker T-ReX LC-QTOF solution (Nova Medical Testing Inc.) was prepared from pooled human blood and injected before sample analysis to check the performance of the LC-MS instruments.
Ion Mode:POSITIVE
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