Evidence map›Paper›PMID 33623106›Full record

ArticleScientific reports2021

Screening of metabolic modulators identifies new strategies to target metabolic reprogramming in melanoma.

Cecilie Abildgaard, Salvatore Rizza, Helle Christiansen, Steffen Schmidt, Christina Dahl, Ahmad Abdul-Al, Annette Christensen, Giuseppe Filomeni, Per Guldberg

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. 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
0.9field-weighted citation impact, top 28% 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, 16 citations in OpenAlex.

  1. Trial
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  4. Thiazolidinedione enhances the efficacy of anti-PD-1 monoclonal antibody in murine melanoma.American journal of physiology. Endocrinology and metabolism · 2024
    Article
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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

9 authors at 5 institutions in 2 countries.

Cecilie AbildgaardMolecular Diagnostics Group, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.
Salvatore RizzaRedox Biology Group, Danish Cancer Society Research Center, Copenhagen, Denmark.
Helle ChristiansenLundbeckfonden Center of Excellence NanoCAN, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Steffen SchmidtLundbeckfonden Center of Excellence NanoCAN, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Christina DahlMolecular Diagnostics Group, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.
Ahmad Abdul-AlMolecular Diagnostics Group, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.
Annette ChristensenMolecular Diagnostics Group, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.
Giuseppe FilomeniRedox Biology Group, Danish Cancer Society Research Center, Copenhagen, Denmark.
Per GuldbergMolecular Diagnostics Group, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark. perg@cancer.dk.
Danish Cancer Society · DKUniversity of Southern Denmark · DKLillebaelt Hospital · DKLundbeck Foundation · DKUniversity of Rome Tor Vergata · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The prognosis of metastatic melanoma remains poor due to de novo or acquired resistance to immune and targeted therapies. Previous studies have shown that melanoma cells have perturbed metabolism and that cellular metabolic pathways represent potential therapeutic targets. To support the discovery of new drug candidates for melanoma, we examined 180 metabolic modulators, including phytochemicals and anti-diabetic compounds, for their growth-inhibitory activities against melanoma cells, alone and in combination with the BRAF inhibitor vemurafenib. Two positive hits from this screen, 4-methylumbelliferone (4-MU) and ursolic acid (UA), were subjected to validation and further characterization. Metabolic analysis showed that 4-MU affected cellular metabolism through inhibition of glycolysis and enhanced the effect of vemurafenib to reduce the growth of melanoma cells. In contrast, UA reduced mitochondrial respiration, accompanied by an increase in the glycolytic rate. This metabolic switch potentiated the growth-inhibitory effect of the pyruvate dehydrogenase kinase inhibitor dichloroacetate. Both drug combinations led to increased production of reactive oxygen species, suggesting the involvement of oxidative stress in the cellular response. These results support the potential use of metabolic modulators for combination therapies in cancer and may encourage preclinical validation and clinical testing of such treatment strategies in patients with metastatic melanoma.

Indexed as

Antineoplastic AgentsCell Line, TumorCell ProliferationDrug DiscoveryGlycolysisHumansHymecromoneMelanomaMitochondriaOxidantsOxidative StressProtein Kinase InhibitorsSmall Molecule LibrariesTriterpenesUrsolic AcidAntineoplastic AgentsHymecromoneOxidantsProtein Kinase InhibitorsSmall Molecule LibrariesTriterpenesUrsolic Acid

Identifiers

PMID33623106
PMCPMC7902673
OpenAlexW3131228342

What OpenQuestion holds

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LicenceCC BY
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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.