PXD043309

PXD043309 is an original dataset announced via ProteomeXchange.

Title	Untargeted Multi-Omics of LNCaP Cell-line Treated with Novel DNA Minor Groove Binder and /or Doxorubicin Using Mass-Spectrometry
Description	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.
HostingRepository	PRIDE
AnnounceDate	2025-11-21
AnnouncementXML	Submission_2025-11-21_11:16:05.366.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Core Facility
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetic acid derivatized residue
Instrument	time-of-flight

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-26 08:27:01	ID requested
⏵ 1	2025-11-21 11:16:05	announced

10.1021/ACS.JPROTEOME.5C00135;

submitter keyword: Metabolomics, TIMS-TOF, Proteomics,Prostate cancer

Mohammad H Semreen
contact affiliation	1 - College of Pharmacy, University of Sharjah, Sharjah 2 - Sharjah Institute for Medical Research, University of Sharjah, Sharjah
contact email	msemreen@sharjah.ac.ae
lab head
Core Facility
contact affiliation	Sharjah Institute for Medical Research, University of Sharjah
contact email	tims-tof@sharjah.ac.ae
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD043309

PRIDE project URI

• PRIDE
  1. PXD043309
     1. Label: PRIDE project
     2. Name: Untargeted Multi-Omics of LNCaP Cell-line Treated with Novel DNA Minor Groove Binder and /or Doxorubicin Using Mass-Spectrometry