Evidence map›Paper›PMID 24008365›Full record

ArticleMolecules and cells2013

Midazolam induces cellular apoptosis in human cancer cells and inhibits tumor growth in xenograft mice.

Siddhartha Kumar Mishra, Ju-Hee Kang, Chang Woo Lee, Seung Hyun Oh, Jun Sun Ryu, Yun Soo Bae, Hwan Mook Kim

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Molecules and cells, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04532606 (Impact of Remimazolam Tosilate for General Anesthesia on Prognosis After Bladder Cancer Surgery), which is not on this map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.3field-weighted citation impact, top 21% 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.

NCT04532606 phase4recruitingnot on this mapstarted 2021, after this paper: background citation

Impact of Remimazolam Tosilate for General Anesthesia on Prognosis After Bladder Cancer Surgery: a Randomized Controlled Trial

TypeinterventionalSponsorPeking University First HospitalRan2021 to 2026Enrolled1,128ConditionsBenzodiazepines, Bladder Cancer, Delirium, SurgeryArmsRemimazolam, Propofol
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Midazolam's Effects on Delayed-Rectifier KInternational journal of molecular sciences · 2021
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Potential for Drug Repositioning of Midazolam for Dentin Regeneration.International journal of molecular sciences · 2019
    Article
  17. Article
  18. Insights into the Roles of Midazolam in Cancer Therapy.Evidence-based complementary and alternative medicine : eCAM · 2017
    Review
  19. TRPM7 channel inhibition mediates midazolam-induced proliferation loss in human malignant glioma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  20. 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

7 authors at 5 institutions in 1 country.

Siddhartha Kumar MishraGachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, 406-840, Korea.
Ju-Hee Kang
Chang Woo Lee
Seung Hyun Oh
Jun Sun Ryu
Yun Soo Bae
Hwan Mook Kim
Gachon University · KRChung-Ang University · KREwha Womans University · KRKorea Research Institute of Bioscience and Biotechnology · KRNational Cancer Center · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Midazolam is a widely used anesthetic of the benzodiazepine class that has shown cytotoxicity and apoptosisinducing activity in neuronal cells and lymphocytes. This study aims to evaluate the effect of midazolam on growth of K562 human leukemia cells and HT29 colon cancer cells. The in vivo effect of midazolam was investigated in BALB/c-nu mice bearing K562 and HT29 cells human tumor xenografts. The results show that midazolam decreased the viability of K562 and HT29 cells by inducing apoptosis and S phase cell-cycle arrest in a concentration-dependent manner. Midazolam activated caspase-9, capspase-3 and PARP indicating induction of the mitochondrial intrinsic pathway of apoptosis. Midazolam lowered mitochondrial membrane potential and increased apoptotic DNA fragmentation. Midazolam showed reactive oxygen species (ROS) scavenging activity through inhibition of NADPH oxidase 2 (Nox2) enzyme activity in K562 cells. Midazolam caused inhibition of pERK1/2 signaling which led to inhibition of the anti-apoptotic proteins Bcl-XL and XIAP and phosphorylation activation of the pro-apoptotic protein Bid. Midazolam inhibited growth of HT29 tumors in xenograft mice. Collectively our results demonstrate that midazolam caused growth inhibition of cancer cells via activation of the mitochondrial intrinsic pathway of apoptosis and inhibited HT29 tumor growth in xenograft mice. The mechanism underlying these effects of midazolam might be suppression of ROS production leading to modulation of apoptosis and growth regulatory proteins. These findings present possible clinical implications of midazolam as an anesthetic to relieve pain during in vivo anticancer drug delivery and to enhance anticancer efficacy through its ROS-scavenging and pro-apoptotic properties.

Indexed as

Adjuvants, AnesthesiaAnimalsAntineoplastic AgentsApoptosisCaspase 3Caspase 9Cell ProliferationFemaleHT29 CellsHumansK562 CellsMembrane GlycoproteinsMembrane Potential, MitochondrialMiceMice, Inbred BALB CMidazolamAdjuvants, AnesthesiaAntineoplastic AgentsCaspase 3Caspase 9CYBB protein, humanMembrane GlycoproteinsMidazolamNADPH Oxidase 2NADPH OxidasesReactive Oxygen Species

Identifiers

PMID24008365
PMCPMC3887981
OpenAlexW1967550589

What OpenQuestion holds

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Registered trials

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.