Summary of Study ST002317
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 PR001485. The data can be accessed directly via it's Project DOI: 10.21228/M8S41S 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 | ST002317 |
| Study Title | Mass spectroscopy‑based proteomics and metabolomics analysis of triple‑positive breast cancer cells treated with tamoxifen |
| Study Summary | HER2-enriched breast cancer with high levels of hormone receptor expression, known as triple positive breast cancer, may represent a new entity with a relatively favourable prognosis against which the combination of chemotherapy, HER-2 inhibition, and endocrine treatment may be considered overtreatment. We explored the effect of the anticancer drugs tamoxifen and trastuzumab, both separately and in combination, on the integrated proteomic and metabolic profile of triple positive breast cancer cells (BT-474). Method We employed ultra-high-performance liquid chromatography-quadrupole time of flight mass spectrometry using a Bruker timsTOF to investigate changes in BT-474 cell line treated with either tamoxifen, trastuzumab or a combination. Differentially abundant metabolites were identified using the Bruker Human Metabolome Database metabolite library and proteins using the Uniprot proteome for Homo sapiens using MetaboScape and MaxQuant, respectively, for identification and quantitation. Results A total of 77 proteins and 85 metabolites were found to significantly differ in abundance in BT-474 treated cells with tamoxifen 5 μM/and or trastuzumab 2.5 μM. Findings suggest that by targeting important cellular signalling pathways which regulate cell growth, apoptosis, proliferation, and chemoresistance, these medicines have a considerable anti-growth effect in BT-474 cells. Pathways enriched for dysregulation include RNA splicing, neutrophil degranulation and activation, cellular redox homeostasis, mitochondrial transmembrane transport, ferroptosis and necroptosis, ABC transporters and central carbon metabolism. Conclusion Our findings in protein and metabolite level research revealed that anti-cancer drug therapy had a significant impact on the key signalling pathways and molecular processes in triple positive BT-474 cell lines. |
| Institute | University of Sharjah |
| Department | Sharjah Institute for Medical Research |
| Laboratory | Biomarker Discovery Group |
| Last Name | Soares |
| First Name | Nelson |
| Address | M32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah |
| nsoares@sharjah.ac.ae | |
| Phone | 065057656 |
| Submit Date | 2022-10-18 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-11-21 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Treatment:
| Treatment ID: | TR002415 |
| Treatment Summary: | Triplicate flasks were prepared for each treatment condition for each analysis (metabolomic and proteomic) for a total of 24 flasks. Two million cells were seeded in each 75 cm2 tissue culture flask and incubated for 24 h. The cells were then treated with Tamoxifen (5 μM) and/or Trastuzumab (2.5 μM) for 24 h. These concentrations correspond to the IC50 of these compounds with BT-474 cells, as determined by cytotoxicity assays (data not shown). Control cells were treated with vehicle (dimethyl sulfoxide (DMSO) at 0.5% for 24 h. Following the incubation period, cells were collected by trypsinization and washed twice with phosphate-buffered saline solution (PBS) before re-suspending in 1 mL 1 × PBS for further analysis. Finally, cells were collected as pellets by centrifugation at 1200 rounds per minute (rpm) for 10 min at room temperature. To negate the effect of Circadian rhythms on the response of cells to treatment, cells were kept under the same conditions during the entire incubation period and the cell collection was done concurrently for all samples. In addition, the same number of cells were used for each sample to avoid the effect of variation in cell numbers. |
| Treatment: | Drugs |
| Treatment Compound: | Tamoxifen and/or Trastuzumab |
