Summary of Study ST002731
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 PR001695. The data can be accessed directly via it's Project DOI: 10.21228/M8MB0X 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 | ST002731 |
| Study Title | Untargeted Multi-Omics of LNCaP Cell-line Treated with Novel DNA Minor Groove Binder and /or Doxorubicin Using Mass-Spectrometry |
| Study Summary | Prostate cancer poses a significant health risk, ranking as the second most common cancer among men in the United States. However, the effectiveness of current anti-prostate cancer drugs is limited due to increasing drug resistance and side effects. Consequently, there is a pressing need to develop new compounds and identify novel drug targets that can surpass these limitations. Due to their targeted mechanism, DNA minor groove binders (MGBs) are becoming more popular as a relatively safe and effective alternative. In our research, we employed multi-omics techniques to investigate the mechanism of action of a novel MGB compound (MGB4) through LC-MS/MS-based untargeted metabolomics combined with discovery proteomics analysis performed on LNCaP cells, which were treated with MGB4, doxorubicin, or a combination of both compounds. Through a one-way ANOVA test with a significance level of p-value < 0.05, we identified 99 metabolites and 1143 proteins associated with the treatments. Our findings indicate that treating LNCaP cells with doxorubicin or the MGB4 lead compound yielded similar effects, albeit not identical, on the cells. Both compounds deactivated the translation pathway in the cells. Furthermore, we observed alterations in sphingolipid and amino acid metabolic pathways, potentially contributing to the suppression of prostate cancer cell proliferation and division. Additionally, doxorubicin and combined treatments resulted in reduced metabolism of spermine and spermidine, likely stemming from decreased protein synthesis of key enzymes involved in their pathways. Moreover, the combined treatment exhibited a synergistic interaction between the two compounds, leading to altered purine metabolism and a more pronounced reduction in metabolite abundance compared to individual treatments. Overall, our study demonstrates the robustness of the multi-omics approach in elucidating the mechanism of action of promising drug candidates. It also suggests that MGB4 shows potential as a candidate for prostate cancer treatment. |
| Institute | Sharjah Institute for Medical Research |
| Last Name | Facility |
| First Name | Core |
| Address | M32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah, Sharjah, UAE, Sharjah, 000, United Arab Emirates |
| tims-tof@sharjah.ac.ae | |
| Phone | +971 6 5057656 |
| Submit Date | 2023-06-07 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-06-25 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO002830 |
| Collection Summary: | Human prostate cancer cells LNCaP were grown in Roswell Park Memorial Institute (RPMI) 1640 Medium (Sigma Aldrich, Germany) supplemented with 10% fetal bovine serum (FBS) (Sigma Aldrich, Germany). A combination of 1 % penicillin and streptomycin antibiotics was added to RPMI/FBS growth media. Cells were maintained in humidified incubator with conditions of 37◦C temperature and 5 % CO2. |
| Sample Type: | LNCaP cells |
| Storage Conditions: | -80℃ |
