2. Academic Validation
  3. Untargeted Multiomics of LNCaP Cell Line Treated with a Novel DNA Minor Groove Binder and/or Doxorubicin Using Mass Spectrometry

Untargeted Multiomics of LNCaP Cell Line Treated with a Novel DNA Minor Groove Binder and/or Doxorubicin Using Mass Spectrometry

  • J Proteome Res. 2025 Oct 3;24(10):4911-4924. doi: 10.1021/acs.jproteome.5c00135.
Ruba A Zenati 1 2,  Nelson C Soares 3 4 5 6,  Hasan Y Alniss 1 2,  Hamza M Al-Hroub 1,  Raafat El-Awady 1 7,  Ahmad Y Abuhelwa 1 7,  Wafaa S Ramadan 1 8,  Shereen M Aleidi 1 2 9,  Waseem El-Huneidi 1 8,  Eman Abu-Gharbieh 1 10,  Karem H Alzoubi 1 7,  Yasser Bustanji 1 8 9,  Mohammad H Semreen 1 2
Affiliations

Affiliations

  • 1 Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.
  • 2 College of Pharmacy, Department of Medicinal Chemistry, University of Sharjah, Sharjah 27272, United Arab Emirates.
  • 3 Center for Applied and Translational Genomics (CATG), Mohammed Bin Rashid University Medicine and Health Sciences (MBRU), Dubai Health, P.O. Box 505055 Dubai, United Arab Emirates.
  • 4 College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Health, P.O. Box 505055 Dubai, United Arab Emirates.
  • 5 Laboratory of Proteomics, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge (INSA), Av Padre Cruz, Lisbon 1649-016, Portugal.
  • 6 Comprehensive Health Research Centre (CHRC), NOVA Medical School, University NOVA of Lisbon, Lisbon 1169-056, Portugal.
  • 7 Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, The University of Sharjah, Sharjah 27272, United Arab Emirates.
  • 8 Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.
  • 9 Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of Jordan, Amman 11942, Jordan.
  • 10 Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.
PMID: 40907013 DOI: 10.1021/acs.jproteome.5c00135
Abstract

Prostate Cancer (PCa) remains a major global health concern, ranking among the most prevalent Cancer in men worldwide. Despite the availability of various therapeutic options, the clinical efficacy of current anti-PCa agents is often compromised by drug resistance and adverse effects. DNA minor groove Binders offer a potential therapeutic alternative, owing to their selective mechanism of action and favorable safety profiles. In the present study, we utilized a multiomics strategy to investigate the molecular impact of novel compound MGB4. LNCaP cells were treated with doxorubicin, MGB4, or a combination of both, followed by LC-MS/MS-based untargeted proteomics and metabolomics analyses. One-way ANOVA (p-value <0.05) revealed 55 significantly dysregulated proteins and 57 altered metabolites across treatments. Our findings indicate that both MGB4 and doxorubicin impacted key cellular pathways, including inhibition of translation and alterations in sphingolipid and amino acid metabolism, while doxorubicin and the combination therapy also reduced spermine and spermidine metabolism. Notably, the combined treatment exhibited synergistic effects, significantly impacting purine metabolism and reducing metabolite levels more than individual therapies. This study provides key molecular insights into MGB4 and doxorubicin's mechanisms, supporting MGB4 as a potential prostate Cancer drug candidate.

Keywords

LC-MS/MS-QTOF; doxorubicin; metabolomics; minor groove binders (MGBs); prostate cancer; proteomics.

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