Investigation of the anticancer molecular pathways of UCPH 101 combined with cerium oxide via hydrothermal synthesis on glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults and exhibits a highly aggressive course, typically associated with fatal outcomes. Despite current multimodal treatment approaches involving surgical resection, radiotherapy, and temozolomide-based chemotherapy, the average survival time remains between 12–15 months, and a complete cure has yet to be developed. The invasive nature of GBM, insufficient blood-brain barrier penetration of drugs, lack of target specificity, significant side effects, and the development of resistance mechanisms against treatment have increased the need for alternative therapeutic strategies. The synergistic effects of UCPH-101, a selective inhibitor of the glutamate transporter EAAT1, and biocompatible cerium oxide (Ce₂O₃) nanoparticles synthesized via the green hydrothermal method were investigated. These nanoparticles were designed to enhance the membrane permeability of UCPH-101 by facilitating its binding to cerium oxide, thereby improving its penetration into glioblastoma multiforme cells and increasing its antineoplastic efficacy. This thesis study was conducted on the U87-MG cell line, and the effects of the applied compounds were evaluated through TALI flow cytometry to determine the ratios of apoptotic, necrotic, and viable cells. Fluorescent staining techniques were employed to visualize intracellular oxidative stress, viable cell count, and apoptotic structures, while Real-Time PCR was used to analyze gene expression levels related to apoptotic pathways, hypoxia-angiogenesis pathways, cytokine signaling, and antioxidant defense mechanisms. The results demonstrated that our candidate drug molecule at a 79 μM dose, compared to temozolomide's IC50 value of 450 μM, exhibited higher gravimetric potency. Additionally, it more effectively induced antioxidant defense mechanisms, apoptotic pathways, and cytokine signaling pathways while potently suppressing angiogenesis and hypoxia-related pathways.