Summary of Study ST002173

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 PR001382. The data can be accessed directly via it's Project DOI: 10.21228/M8312X This work is supported by NIH grant, U2C- DK119886.

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Study IDST002173
Study TitleUnveiling the mechanism of action of nature-inspired anti-cancer compounds using a multi-Omics approach
Study SummaryNovel anti-cancer compounds SIMR-3058 and SIMR-3066 were tested against MCF-7. The 2020 global cancer registry has ranked breast cancer (BCa) as the most commonly diagnosed type of cancer and the most common cause of cancer-related deaths, especially in women worldwide. Increased resistance and significant side effects continue to limit the efficacy of anti-BCa drugs, hence the need to identify new drug targets and to develop novel compounds to overcome these limitations. Nature-inspired anti-cancer compounds are becoming increasingly popular since they often provide a relatively safe and effective alternative. In this study, we employed multi-omics techniques to gain insights into the novel and potentially relevant mechanism of action of two recently identified nature- inspired anti-cancer compounds (SIMR 3066 and SIMR 3058). Discovery proteomics analysis combined with LC-MS/MS-based untargeted metabolomics analysis was performed on compound-treated vs. DMSO-treated control MCF-7 cells. Downstream protein functional analysis showed that most of the responsive proteins were functionally associated with antigen processing and neutrophil degranulation, RNA catabolism and protein folding as well as cytoplasmic vesicle lumen and mitochondrial matrix formation. Consistent with the proteomics findings, metabolomic pathway analysis suggested that SIMR compounds could alter metabolic pathways such as glycolysis, the Krebs cycle and oxidative phosphorylation. Furthermore, metabolomics-based enriched-for-action pathway analysis showed that the of two SIMR compounds associate with mercaptopurine and thioguanine and azathiprine. Lastly, joint proteomics and metabolomics analysis revealed that treatment of BCa with SIMR3066 disrupts several signaling pathways including such p53-mediated apoptosis and the circadian entertainment pathway. Overall, the multi-omics we used in this study seems potent at probing the mechanism of action of novel anti-cancer agents.
Institute
University of Sharjah
DepartmentSharjah Institute for Medical Research
LaboratoryBiomarker Discovery Group
Last NameGiddey
First NameAlexander
AddressSharjah
Emailagiddey@sharjah.ac.ae
Phone+971 6 5057417
Submit Date2022-04-06
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2023-05-01
Release Version1
Alexander Giddey Alexander Giddey
https://dx.doi.org/10.21228/M8312X
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA2089243058(4)-02_15_1_7553058
SA2089253058(2)-02_13_1_7513058
SA2089263058(5)-02_16_1_7573058
SA2089273058(4)-01_15_1_7543058
SA2089283058(3)-02_14_1_7533058
SA2089293058(1)-02_12_1_7493058
SA2089303058(2)-01_13_1_7503058
SA2089313058(1)-01_12_1_7483058
SA2089323058(3)-01_14_1_7523058
SA2089333058(5)-01_16_1_7563058
SA2089343066(2)-01_8_1_7403066
SA2089353066(1)-01_7_1_7383066
SA2089363066(3)-02_9_1_7433066
SA2089373066(3)-01_9_1_7423066
SA2089383066(2)-02_8_1_7413066
SA2089393066(4)-01_10_1_7443066
SA2089403066(4)-02_10_1_7453066
SA2089413066(5)-02_11_1_7473066
SA2089423066(5)-01_11_1_7463066
SA2089433066(1)-02_7_1_7393066
SA208944CR4-02_5_1_735Control
SA208945CR2-01_3_1_730Control
SA208946CR1-02_2_1_729Control
SA208947CR1-01_2_1_728Control
SA208948CR2-02_3_1_731Control
SA208949CR3-01_4_1_732Control
SA208950CR5-01_6_1_736Control
SA208951CR4-01_5_1_734Control
SA208952CR3-02_4_1_733Control
SA208953CR5-02_6_1_737Control
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