Open AccessDiazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line
Author(s) -
Drljača Jovana,
Popović Aleksandra,
Bulajić Dragica,
Stilinović Nebojša,
Vidičević Novaković Sašenka,
Sekulić Slobodan,
Milenković Ivan,
Ninković Srđan,
Ljubković Marko,
Čapo Ivan
Publication year - 2022
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13889
Subject(s) - temozolomide , medicine , concomitant , pharmacology , apoptosis , cell cycle , cell cycle checkpoint , oncology , chemotherapy , biology , cancer , biochemistry
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 electron transport chain, as well as the activities of complexes I and II, vs. TMZ alone ( p < 0.001). Conclusion Comparing our results with data reported that DIA elicits cell cycle arrest in the G0/G1 phase and favors senescence reveals that DIA diminishes TMZ efficacy in concomitant use in the treatment of GBM. However, due to its great potency to hinder GBM proliferation and metabolism, it could be considered using DIA as maintenance therapy after TMZ cycles.