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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST002173 |
| Study Title | Unveiling the mechanism of action of nature-inspired anti-cancer compounds using a multi-Omics approach |
| Study Summary | Novel 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 |
| Department | Sharjah Institute for Medical Research |
| Laboratory | Biomarker Discovery Group |
| Last Name | Giddey |
| First Name | Alexander |
| Address | Sharjah |
| agiddey@sharjah.ac.ae | |
| Phone | +971 6 5057417 |
| Submit Date | 2022-04-06 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-05-01 |
| Release Version | 1 |
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Subject:
| Subject ID: | SU002259 |
| Subject Type: | Cultured cells |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Cell Strain Details: | MCF-7 |
| Species Group: | Mammals |
