Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line

Abstract

Aims: Many patients with glioblastoma (GBM) suffer from comorbid neurological/ psychiatric disorders and, therefore, are treated with psychopharmacological agents. Diazepam (DIA) is widely adopted to treat status epilepticus, alleviate anxiety, and inhibit chemotherapy-associated delayed emesis in GBM patients. Even though temozolomide (TMZ) and DIA could be found as possible combination therapy in clinical practice, there are no reports of their combined effects in GBM. Hence, it may be of interest to investigate whether DIA enhances the antitumor efficacy of TMZ in GBM cells.Methods: U87 human GBM was used to examine the effects of combined TMZ and DIA on cell viability, and the oxygen consumption within the cells, in order to evaluate mitochondrial bioenergetic response upon the treatment. Results:The cooperative index showed the presence of antagonism between TMZ and DIA, which was confirmed on long-term observation. Moreover, the level of apoptosis after the TMZ treatment was significantly decreased when administered with DIA (p < 0.001). Concomitant use of TMZ and DIA increased the basal cell respiration rate, the oxidative phosphorylation rate, and maximal capacity of mitochondrial

Synthesis of Bleomycin-Inspired RNA Ligands Targeting the Biogenesis of Oncogenic miRNAs

“…We thus decided to assess antiproliferative activity of the synthesized compounds in cancer cells, measuring the effect of all compounds on the cell viability of the U87 glioblastoma cell line. It has been largely demonstrated in the literature that this cell line overexpresses miR-21, miR-18a, and miR148a. , Among all synthesized compounds, only 1 , 9g , and 11c were able to inhibit the proliferation of U87 cells with IC 50 values of 37.4 μM for 1 , 45.3 μM for 9g , and 16.5 μM for 11c (Table and Figure S7 in the Supporting Information) while the IC 50 of TMZ is reported to be over 100 μM. , All compounds were also tested on MCR5 fibroblasts to assess the potential off-target toxicity of the active compounds on healthy cells. Compound 1 is also toxic on healthy cells, showing the same IC 50 value on MCR5 cells, compound 9g shows a 30% inhibition of proliferation at 50 μM while 11c is not toxic for MCR5 in the range of tested concentrations.…”

“…14,32 Among all synthesized compounds, only 1, 9g, and 11c were able to inhibit the proliferation of U87 cells with IC 50 values of 37.4 μM for 1, 45.3 μM for 9g, and 16.5 μM for 11c (Table 2 and Figure S7 in the Supporting Information) while the IC 50 of TMZ is reported to be over 100 μM. 33,34 All compounds were also tested on MCR5 fibroblasts to assess the potential off-target toxicity of the active compounds on healthy cells. Compound 1 is also toxic on healthy cells, showing the same IC 50 value on MCR5 cells, compound 9g shows a 30% inhibition of proliferation at 50 μM while 11c is not toxic for MCR5 in the range of tested concentrations.…”

The effect of Azo-dyes on glioblastoma cells in vitro

“…At the moment, this alkylating agent has been widely used to treat GB, and many methods have been developed both to enhance its activity and to reduce the chemoresistance ( Akbarnejad et al, 2017 , Gerlach et al, 2022 , Kang et al, 2022 , Shao et al, 2019 ). Also, attention must be paid to concomitant administration of other medication, due to their influence on the TMZ efficacy ( Drljača et al, 2022 ). Different strategies have been used to elucidate the TMZ influence on cancer cells.…”