Evidence map›Paper›PMID 36144606›Full record

ArticleMolecules (Basel, Switzerland)2022

EPR Investigations to Study the Impact of Mito-Metformin on the Mitochondrial Function of Prostate Cancer Cells.

Donatienne d'Hose, Barbara Mathieu, Lionel Mignion, Micael Hardy, Olivier Ouari, Bénédicte F Jordan, Pierre Sonveaux, Bernard Gallez

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 36% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
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  5. OXPHOS-targeting drugs in oncology: new perspectives.Expert opinion on therapeutic targets
    Review
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

8 authors at 3 institutions in 2 countries.

Donatienne d'HoseBiomedical Magnetic Resonance, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.
Barbara MathieuBiomedical Magnetic Resonance, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.
Lionel MignionBiomedical Magnetic Resonance, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.ORCID 0000-0002-9426-8600
Micael HardyInstitut de Chimie Radicalaire UMR 7273, Aix-Marseille Université/CNRS, 13013 Marseille, France.ORCID 0000-0003-2976-7785
Olivier OuariInstitut de Chimie Radicalaire UMR 7273, Aix-Marseille Université/CNRS, 13013 Marseille, France.
Bénédicte F JordanBiomedical Magnetic Resonance, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.ORCID 0000-0002-7126-2206
Pierre SonveauxPole of Pharmacology and Therapeutics, Institut de Recherches Expérimentales et Cliniques (IREC), Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.ORCID 0000-0001-6484-8834
Bernard GallezBiomedical Magnetic Resonance, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.ORCID 0000-0002-5708-1302
UCLouvain · BECentre National de la Recherche Scientifique · FRWalloon Excellence in Lifesciences and Biotechnology · BE

Funding

Actions de Recherche Concertées program of the Communauté Française de Belgique ARC 21-26/118Fonds National de la Recherche Scientifique J008220F
6 · The paper itself

Abstract

backgroundMito-metformin10 (MM10), synthesized by attaching a triphenylphosphonium cationic moiety via a 10-carbon aliphatic side chain to metformin, is a mitochondria-targeted analog of metformin that was recently demonstrated to alter mitochondrial function and proliferation in pancreatic ductal adenocarcinoma. Here, we hypothesized that this compound may decrease the oxygen consumption rate (OCR) in prostate cancer cells, increase the level of mitochondrial ROS, alleviate tumor hypoxia, and radiosensitize tumors.

methodsOCR and mitochondrial superoxide production were assessed by EPR (9 GHz) in vitro in PC-3 and DU-145 prostate cancer cells. Reduced and oxidized glutathione were assessed before and after MM10 exposure. Tumor oxygenation was measured in vivo using 1 GHz EPR oximetry in PC-3 tumor model. Tumors were irradiated at the time of maximal reoxygenation.

results24-hours exposure to MM10 significantly decreased the OCR of PC-3 and DU-145 cancer cells. An increase in mitochondrial superoxide levels was observed in PC-3 but not in DU-145 cancer cells, an observation consistent with the differences observed in glutathione levels in both cancer cell lines. In vivo, the tumor oxygenation significantly increased in the PC-3 model (daily injection of 2 mg/kg MM10) 48 and 72 h after initiation of the treatment. Despite the significant effect on tumor hypoxia, MM10 combined to irradiation did not increase the tumor growth delay compared to the irradiation alone.

conclusionsMM10 altered the OCR in prostate cancer cells. The effect of MM10 on the superoxide level was dependent on the antioxidant capacity of cell line. In vivo, MM10 alleviated tumor hypoxia, yet without consequence in terms of response to irradiation.

Indexed as

MetforminPancreatic NeoplasmsProstatic NeoplasmsAntioxidantsCarbonCell Line, TumorGlutathione DisulfideHumansMaleMitochondriaReactive Oxygen SpeciesSuperoxidesAntioxidantsCarbonGlutathione DisulfideMetforminReactive Oxygen SpeciesSuperoxidescancerEPRESRirradiationmitochondrial ROSoximetryoxygen consumptiontumor hypoxiatumor oxygenation

Identifiers

PMID36144606
PMCPMC9504708
OpenAlexW4296010675

What Socratic 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 Socratic graph.