Evidence map›Paper›PMID 36359862›Full record

ArticleCells2022

Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma.

Beatriz I Fernandez-Gil, Andrea Otamendi-Lopez, Alexandra Bechtle, Carla A Vazquez-Ramos, Neda Qosja, Paola Suarez-Meade, Rachel Sarabia-Estrada, Mark E Jentoft, Hugo Guerrero-Cázares, Germaine Escames and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 37% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Glioblastoma Metabolism: Insights and Therapeutic Strategies.International journal of molecular sciences · 2023
    Review
  11. 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

12 authors at 2 institutions in 2 countries.

Beatriz I Fernandez-GilDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.ORCID 0000-0003-2347-2687
Andrea Otamendi-LopezDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Alexandra BechtleDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Carla A Vazquez-RamosDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Neda QosjaDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Paola Suarez-MeadeDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Rachel Sarabia-EstradaDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Mark E JentoftDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL 32224, USA.
Hugo Guerrero-CázaresDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.ORCID 0000-0003-1307-719X
Germaine EscamesInstituto de Biotecnología Centro de Investigación Biomédica, Universidad de Granada, 18016 Granada, Spain.ORCID 0000-0003-1256-7656
Paula SchiapparelliDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Alfredo Quiñones-HinojosaDepartment of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Mayo Clinic in Florida · USUniversidad de Granada · ES

Funding

Intra-Operative, Label-Free Detection of Brain Cancer Infiltration with Quantitative Optical ImagingR01CA200399 · NCI · JOHNS HOPKINS UNIVERSITY · PI LI, XINGDE, QUINONES-HINOJOSA, ALFREDO · 2016 to 2020
$3.0M
NCI NIH HHS R01 CA200399
6 · The paper itself

Abstract

Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin's functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin's cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.

Indexed as

GlioblastomaMelatoninAnimalsCell DivisionGlycolysisHumansHydrogen-Ion ConcentrationMiceMelatonincancer metabolismGBMglycolysisintracellular aciditylactateLDHAMCT4OXPHOSROS

Identifiers

PMID36359862
PMCPMC9654239
OpenAlexW4309091372

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.