Evidence map›Paper›PMID 35689667›Full record

ArticleMetallomics : integrated biometal science2022

A ferrocene-containing nucleoside analogue targets DNA replication in pancreatic cancer cells.

Marium Rana, Alessio Perotti, Lucy M Bisset, James D Smith, Emma Lamden, Zahra Khan, Media K Ismail, Katherine Ellis, Katie A Armstrong, Samantha L Hodder and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Metallomics : integrated biometal science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Molecules (Basel, Switzerland) · 2024
    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

17 authors.

Marium RanaSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Alessio PerottiSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Lucy M BissetSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
James D SmithSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Emma LamdenSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Zahra KhanSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Media K IsmailDepartment of pharmacy, college of pharmacy, Knowledge University, 44001 Erbil, Kurdistan Region, Iraq.
Katherine EllisInstitute of Cancer and Genomic Sciences, and The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Katie A ArmstrongSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Samantha L HodderSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Cosetta BertoliMRC Laboratory or Molecular Cell Biology, University College London, London, WC1E 6BT, UK.
Leticia MeneguelloMRC Laboratory or Molecular Cell Biology, University College London, London, WC1E 6BT, UK.
Robertus A M de BruinMRC Laboratory or Molecular Cell Biology, University College London, London, WC1E 6BT, UK.
Joanna R MorrisInstitute of Cancer and Genomic Sciences, and The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Isolda Romero-CanelonSchool of Pharmacy, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
James H R TuckerSchool of Chemistry, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Nikolas J HodgesSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

Funding

Cancer Research UK 20147Medical Research CouncilWellcome Trust 206343/Z/17/Z
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a disease that remains refractory to existing treatments including the nucleoside analogue gemcitabine. In the current study we demonstrate that an organometallic nucleoside analogue, the ferronucleoside 1-(S,Rp), is cytotoxic in a panel of PDAC cell lines including gemcitabine-resistant MIAPaCa2, with IC50 values comparable to cisplatin. Biochemical studies show that the mechanism of action is inhibition of DNA replication, S-phase cell cycle arrest and stalling of DNA-replication forks, which were directly observed at single molecule resolution by DNA-fibre fluorography. In agreement with this, transcriptional changes following treatment with 1-(S,Rp) include activation of three of the four genes (HUS1, RAD1, RAD17) of the 9-1-1 check point complex clamp and two of the three genes (MRE11, NBN) that form the MRN complex as well as activation of multiple downstream targets. Furthermore, there was evidence of phosphorylation of checkpoint kinases 1 and 2 as well as RPA1 and gamma H2AX, all of which are considered biochemical markers of replication stress. Studies in p53-deficient cell lines showed activation of CDKN1A (p21) and GADD45A by 1-(S,Rp) was at least partially independent of p53. In conclusion, because of its potency and activity in gemcitabine-resistant cells, 1-(S,Rp) is a promising candidate molecule for development of new treatments for PDAC.

Indexed as

DNA ReplicationNucleosidesPancreatic NeoplasmsCell Cycle ProteinsDNA-Binding ProteinsDNA DamageHumansMetallocenesS PhaseTumor Suppressor Protein p53Cell Cycle ProteinsDNA-Binding ProteinsMetallocenesNucleosidesRad17 protein, humanTumor Suppressor Protein p53DNA replicationFerrocenenucleoside analoguepancreatic cancerreplication fork arrest

Identifiers

PMID35689667
PMCPMC9320222

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.