Multi-omics analysis revealed significant metabolic changes in brain cancer cells treated with paclitaxel and/or topotecan
Ahlam M. Semreen,
Leen Oyoun Alsoud,
Mohammad H. Semreen,
Munazza Ahmed,
Hamza M. Al-Hroub,
Raafat El-Awady,
Wafaa S. Ramadan,
Ahmad Abuhelwa,
Yasser Bustanji,
Nelson C. Soares,
Karem H. Alzoubi
Affiliations
Ahlam M. Semreen
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
Leen Oyoun Alsoud
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
Mohammad H. Semreen
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
Munazza Ahmed
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
Hamza M. Al-Hroub
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
Raafat El-Awady
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
Wafaa S. Ramadan
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
Ahmad Abuhelwa
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
Yasser Bustanji
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; School of Pharmacy, The University of Jordan, Amman, 11942, Jordan; Department of Basic and Clinical Pharmacology, College of Medicine, University of Sharjah, Sharjah, 27272, United Arab Emirates
Nelson C. Soares
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Center for Applied and Translational Genomics (CATG), Mohamed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Health, Dubai, United Arab Emirates; College of Medicine, Mohamed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Health, Dubai, United Arab Emirates; Corresponding author. Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Karem H. Alzoubi
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; Corresponding author. Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Glioblastoma (GBM) stands as the most common primary malignant brain tumor. Despite the best standard therapies, GBM survivors have a brief survival time, about 24 months on average. The treatment is troublesome because the cancer cells may not respond well to specific therapies as they grow within an extensive network of blood vessels. Our study aims to evaluate the impact of paclitaxel 5.3 μg/mL and topotecan 0.26 μM solely and in pairwise combination on the resultant metabolic and proteomic signatures of the U87 cell line while using the precise ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF) analytical technology. The U87 cells wear treated with DMSO, paclitaxel 5.3 μM, topotecan 0.26 μM, and their combinations. Using One-way ANOVA, we observed 14 significantly altered metabolites compared to those cells treated with DMSO. For combination treatment (paclitaxel and topotecan), 11 metabolites were significantly dysregulated. Sparse partial least squares-discriminant analysis (sPLS-DA) revealed minimal overlap, highlighting distinctions among the four groups. While for proteomics, a total of 79 proteins were significantly dysregulated among the groups. These findings can aid in identifying new biomarkers associated with the utilized drugs and creating a map for targeted therapy. EIF3F, GNB2L1, HINT2, and RPA3 were shown to be significantly upregulated in the combination group relative to the control. Moreover, ribosome, apoptosis, HIF-1 signaling, arginine and proline, glutathione, purine metabolism, apelin signaling pathway, and glycolysis were significantly altered in the combination group. Overall, this study underscores the effectiveness of multi-omics approaches in revealing the molecular mechanisms driving chemotherapy responses in cancer cells. Additionally, this work generates a comprehensive list of molecular alterations that can serve as a foundation for further investigations and inform personalized healthcare strategies to enhance patient outcomes.
