Evidence map›Paper›PMID 35216470›Full record

ArticleInternational journal of molecular sciences2022

Proline Dehydrogenase/Proline Oxidase (PRODH/POX) Is Involved in the Mechanism of Metformin-Induced Apoptosis in C32 Melanoma Cell Line.

Ilona Oscilowska, Karol Rolkowski, Weronika Baszanowska, Thi Yen Ly Huynh, Sylwia Lewoniewska, Magdalena Nizioł, Magdalena Sawicka, Katarzyna Bielawska, Paweł Szoka, Wojciech Miltyk and 1 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 19% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
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  4. Life Factors and Melanoma: From the Macroscopic State to the Molecular Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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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

11 authors at 1 institution in 1 country.

Ilona OscilowskaDepartment of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.ORCID 0000-0002-7934-6973
Karol RolkowskiDepartment of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.
Weronika BaszanowskaDepartment of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.
Thi Yen Ly HuynhDepartment of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.
Sylwia LewoniewskaDepartment of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.
Magdalena NiziołDepartment of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.ORCID 0000-0002-8641-2991
Magdalena SawickaDepartment of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.
Katarzyna BielawskaDepartment of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.
Paweł SzokaDepartment of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.
Wojciech MiltykDepartment of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.ORCID 0000-0001-5150-6093
Jerzy PalkaDepartment of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.ORCID 0000-0002-8476-2023
Medical University of Białystok · PL

Funding

European Union No 754432European Union POWR.03.02.00-00-I051/16National Science Center 2017/25/B/NZ7/02183
6 · The paper itself

Abstract

The role of proline dehydrogenase/proline oxidase (PRODH/POX) in the mechanism of antineoplastic activity of metformin (MET) was studied in C32 melanoma cells. PRODH/POX is a mitochondrial enzyme-degrading proline that is implicated in the regulation of cancer cell survival/apoptosis. The enzyme is activated by AMP kinase (AMPK). It has been found that MET induced a significant decrease in cell viability and DNA biosynthesis accompanied by an increase in the expressions of AMPK and PRODH/POX in C32 cells. The mechanism for MET-dependent cytotoxicity on C32 cells was found at the level of PRODH/POX-induced ROS generation and activation of Caspase-3 and Caspase-9 expressions in these cells. The effects were not observed in MET-treated PRODH/POX knock-out C32 cells. Of interest is an MET-dependent increase in the concentration of proline, which is a substrate for PRODH/POX. This phenomenon is due to the MET-dependent inhibition of collagen biosynthesis, which is the main proline-utilizing process. It has been found that the underlying mechanism of anticancer activity of MET involves the activation of AMPK, PRODH/POX, increase in the cytoplasmic concentration of proline, inhibition of collagen biosynthesis, and stimulation of PRODH/POX-dependent ROS generation, which initiate the apoptosis of melanoma cells.

Indexed as

ApoptosisAMP-Activated Protein KinasesAntineoplastic AgentsCell Line, TumorHumansMelanomaMetforminMitochondriaProline OxidaseAMP-Activated Protein KinasesAntineoplastic AgentsMetforminProline OxidaseAMPKmelanomametforminPRODH/POXproline dehydrogenaseproline oxidase

Identifiers

PMID35216470
PMCPMC8876342
OpenAlexW4212862624

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.