Anastasis in Glioblastoma, Brain Cancer Stem, and Brain Stem Cells

Abstract

Objective: Anastasis, a process that has been discovered recently, halts apoptosis, and thus, recovers the survival functions of cells. It may be suggested that anastasis is related to cancer progression, especially in cancer stem cells which are responsible for therapy resistance, metastasis, and recurrence. In this study, the investigation of the anastasis phenomena and its effect on stemness related gene expressions of brain cancer-related cells are aimed. Methods: In this study commercially obtained glioblastoma multiforme(GBM), brain cancer stem cells(BCSC), and brain stem cells(BSC) were used for in vitro models. To induction of apoptosis 4% ethanol-including medium was used. Annexin V assay was used for confirmation of apoptotic and anastatic status. Gene expression profile was determined real-time qRT-PCR method and fold changes were calculated by using 2-∆∆Ct method. Ingenuity Pathway Analysis was used for the functional pathway and upstream regulatory analysis. Results: A common decrease in the expression of stemness related genes in GBM cells was determined by real-time qRT-PCR performed on anastatic cells. Although BSCs showed a similar expression profile with GBM cells, all stemness genes were upregulated in BCSCs. Similar to expression profile, the canonical pathways were markedly down-regulated in BSC and GBM, while they were up-regulated in BCSC. Differently, it is determined that the activation of self-renewal in GBM and BCSC, unlike BSC. Conclusion: We have demonstrated that the inhibition of anastasis may be used to prevent the malignant transformation of healthy stem cells and the aggression of cancerous stem cells. Anastasis may be suggested as a critical mechanism that supports uncurable cancers.