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The potential use of tideglusib as an adjuvant radio-therapeutic treatment for glioblastoma multiforme cancer stem-like cells.

Pharmacological reports : PR (2020-11-04)
Jolie Bou-Gharios, Sahar Assi, Hisham F Bahmad, Hussein Kharroubi, Tarek Araji, Reda M Chalhoub, Farah Ballout, Hayat Harati, Youssef Fares, Wassim Abou-Kheir

Glioblastoma multiforme (GBM), a stage IV astrocytoma, is the most common brain malignancy among adults. Conventional treatments of surgical resection followed by radio and/or chemotherapy fail to completely eradicate the tumor. Resistance to the currently available therapies is mainly attributed to a subpopulation of cancer stem cells (CSCs) present within the tumor bulk that self-renew leading to tumor relapse with time. Therefore, identification of characteristic markers specific to these cells is crucial for the development of targeted therapies. Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase, is deregulated in a wide range of diseases, including cancer. In GBM, GSK-3β is overexpressed and its suppression in vitro has been shown to induce apoptosis of cancer cells. In our study, we assessed the effect of GSK-3β inhibition with Tideglusib (TDG), an irreversible non-ATP competitive inhibitor, using two human GBM cell lines, U-251 MG and U-118 MG. In addition, we combined TDG with radiotherapy to assess whether this inhibition enhances the effect of standard treatment. Our results showed that TDG significantly reduced cell proliferation, cell viability, and migration of both GBM cell lines in a dose- and time-dependent manner in vitro. Treatment with TDG alone and in combination with radiation significantly decreased the colony formation of U-251 MG cells and the sphere formation of both cell lines, by targeting and reducing their glioblastoma cancer stem-like cells (GSCs) population. Finally, cells treated with TDG showed an increased level of unrepaired radio-induced DNA damage and, thus, became sensitized toward radiation. In conclusion, TDG has proven its effectiveness in targeting the cancerous properties of GBM in vitro and may, hence, serve as a potential adjuvant radio-therapeutic agent to better target this deadly tumor.

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Dulbecco′s Phosphate Buffered Saline, Modified, without calcium chloride and magnesium chloride, liquid, sterile-filtered, suitable for cell culture
Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
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Dulbecco′s Modified Eagle′s Medium/Nutrient Mixture F-12 Ham, With L-glutamine, 15 mM HEPES, and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Fetal Bovine Serum, Heat Inactivated, non-USA origin, sterile-filtered, suitable for cell culture