Evidence map›Paper›PMID 35703405›Full record

ArticleCNS neuroscience & therapeutics2022

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

Jovana Drljača, Aleksandra Popović, Dragica Bulajić, Nebojša Stilinović, Sašenka Vidičević Novaković, Slobodan Sekulić, Ivan Milenković, Srđan Ninković, Marko Ljubković, Ivan Čapo

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  5. Review of the Interactions Between Anesthetic Agents and Chemotherapeutic Agents in Cancer Cell Lines Studied In Vitro.Medical science monitor : international medical journal of experimental and clinical research · 2025
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  6. Unlocking the Unique Potential ofPlants (Basel, Switzerland) · 2024
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  8. HANSynergy: Heterogeneous Graph Attention Network for Drug Synergy Prediction.Journal of chemical information and modeling · 2024
    Article
  9. The effect of Azo-dyes on glioblastoma cellsSaudi journal of biological sciences · 2023
    Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 4 countries.

Jovana DrljačaDepartment of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.ORCID 0000-0003-3785-4897
Aleksandra PopovićCenter for Medical and Pharmaceutical Investigations and Quality Control, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Dragica BulajićCenter for Medical and Pharmaceutical Investigations and Quality Control, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Nebojša StilinovićDepartment of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Sašenka Vidičević NovakovićInstitute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia.
Slobodan SekulićDepartment of Neurology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Ivan MilenkovićDepartment of Neurology, Medical University of Vienna, Vienna, Austria.
Srđan NinkovićDepartment of Surgery, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Marko LjubkovićDepartment of Physiology, University of Split School of Medicine, Split, Croatia.
Ivan ČapoCenter for Medical and Pharmaceutical Investigations and Quality Control, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
University of Novi Sad · RSMedical University of Vienna · ATUniversity of Belgrade · RSUniversity of Split · HR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsMany 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.

methodsU87 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.

resultsThe 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).

conclusionComparing 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.

Indexed as

Brain NeoplasmsGlioblastomaAntineoplastic Agents, AlkylatingApoptosisCell Line, TumorCell ProliferationDiazepamDrug Resistance, NeoplasmHumansTemozolomideXenograft Model Antitumor AssaysAntineoplastic Agents, AlkylatingDiazepamTemozolomideantineoplastic agentdrug interactionsmitochondriaoxidative phosphorylationU87 glioblastoma

Identifiers

PMID35703405
PMCPMC9344091
OpenAlexW4282928336

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.