Reversing glioma malignancy: a new look at the role of antidepressant drugs as adjuvant therapy for glioblastoma multiforme

Cancer Chemotherapy and Pharmacology
Anna M Bielecka-WajdmanE Obuchowicz

Abstract

The role of glioma stem cells (GSCs) in cancer progression is currently debated; however, it is hypothesised that this subpopulation is partially responsible for therapeutic resistance observed in glioblastoma multiforme (GBM). Recent studies have shown that the current treatments not only fail to eliminate the GSC population but even promote GSCs through reprogramming of glioma non-stem cells to stem cells. Since the standard GBM treatment often requires supplementation with adjuvant drugs such as antidepressants, their role in the regulation of the heterogeneous nature of GSCs needs evaluation. We examined the effects of imipramine, amitriptyline, fluoxetine, mirtazapine, agomelatine, escitalopram, and temozolomide on the phenotypic signature (CD44, Ki67, Nestin, Sox1, and Sox2 expression) of GSCs isolated from a human T98G cell line. These drugs were examined in several models of hypoxia (1% oxygen, 2.5% oxygen, and a hypoxia-reoxygenation model) as compared to the standard laboratory conditions (20% oxygen). We report that antidepressant drugs, particularly imipramine and amitriptyline, modulate plasticity, silence the GSC profile, and partially reverse the malignant phenotype of GBM. Moreover, we observed that, in contrast...Continue Reading

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Citations

Sep 15, 2018·Cancer Control : Journal of the Moffitt Cancer Center·Anna M Bielecka-WajdmanEwa Obuchowicz
Apr 5, 2018·Frontiers in Pharmacology·Sze Kiat TanNagi G Ayad
Jul 3, 2021·Fundamental & Clinical Pharmacology·Banafshe AbadiHamid-Reza Rahimi

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