Yüksek verim ve düşük toksisiteli glioblastoma multiforme (GBM) tedavi modellerinin geliştirilmesi

One of the most common types of primary brain tumors, glioblastoma (GBM), is famous for having an aggressive character because of its relatively short median overall life of only 15 months. The gold-standard drug now used in clinics, temozolomide (TMZ), is administered after radiation and surgery to remove the tumor as part of the conventional treatment for GBM. Moreover, the biological complexity of GBM genetic phenotype and resistance that develops against TMZ are the two common challenges that limit effective treatment and, therefore, hinder achieving therapeutic outcomes. Strong interest was raised in pharmacological ascorbate based on the recent clinical research studies that reported its role in improving quality of life and extending survival in a variety of cancer types. Likewise, boron compounds are also being increasingly recognized for its anti-cancer properties. In the current study, the anti-cancer effect of Vitamin-C, sodium pentaborate pentahydrate, and their combination are addressed in the in vitro GBM models of IDH-MUT-U87 and U373MG cell lines. These compounds were examined in terms of understanding their effects on various cellular processes, including apoptosis, autophagy, cell migration, cell cycle, and DNA Damage Response (DDR). Furthermore, in the second part of the study, a combination of Olaparib and Vitamin-C was identified to exert a synergistic effect in cell toxicity measurements. Strikingly, we also observed that the combination of Vitamin-C and NaB promoted an anti-tumorigenic effect through activation of DDR signaling, induction of autophagy, and apoptosis mechanism in the IDH-MUT-U87 cell line. Finally, various combinations of these compounds exhibited anti-cancer effect via DDR and ROS-dependent signaling in the U373MG cell line. In this study, the anti-cancer effect of the combination of NaB and Vitamin-C in GBM cancer models was highlighted. The results of this study may offer an insight into the potential use of the combination of NaB and Vitamin-C as a drug to treat cancer.