Differential anti-tumour effects of MTH1 inhibitors in patient-derived 3D colorectal cancer cultures View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Lizet M. van der Waals, Jamila Laoukili, Jennifer M. J. Jongen, Danielle A. Raats, Inne H. M. Borel Rinkes, Onno Kranenburg

ABSTRACT

Reactive oxygen species (ROS) function as second messengers in signal transduction, but high ROS levels can also cause cell death. MTH1 dephosphorylates oxidized nucleotides, thereby preventing their incorporation into DNA and protecting tumour cells from oxidative DNA damage. Inhibitors of MTH1 (TH588 and (S)-crizotinib) were shown to reduce cancer cell viability. However, the MTH1-dependency of the anti-cancer effects of these drugs has recently been questioned. Here, we have assessed anti-tumour effects of TH588 and (S)-crizotinib in patient-derived 3D colorectal cancer cultures. Hypoxia and reoxygenation - conditions that increase intracellular ROS levels - increased sensitivity to (S)-crizotinib, but not to TH588. (S)-crizotinib reduced tyrosine phosphorylation of c-MET and ErbB3 whereas TH588 induced a mitotic cell cycle arrest, which was not affected by adding ROS-modulating compounds. Furthermore, we show that both compounds induced DNA damage that could not be prevented by adding the ROS inhibitor N-acetyl-L-cysteine. Moreover, adding ROS-modulating compounds did not alter the reduction in viability in response to TH588 and (S)-crizotinib. We conclude that TH588 and (S)-crizotinib have very clear and distinct anti-tumour effects in 3D colorectal cancer cultures, but that these effects most likely occur through distinct and ROS-independent mechanisms. More... »

PAGES

819

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-37316-w

DOI

http://dx.doi.org/10.1038/s41598-018-37316-w

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111676556

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30692572


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University Medical Center Utrecht", 
          "id": "https://www.grid.ac/institutes/grid.7692.a", 
          "name": [
            "Laboratory Translational Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "van der Waals", 
        "givenName": "Lizet M.", 
        "id": "sg:person.012645335613.60", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012645335613.60"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University Medical Center Utrecht", 
          "id": "https://www.grid.ac/institutes/grid.7692.a", 
          "name": [
            "Laboratory Translational Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Laoukili", 
        "givenName": "Jamila", 
        "id": "sg:person.01030512251.67", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01030512251.67"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University Medical Center Utrecht", 
          "id": "https://www.grid.ac/institutes/grid.7692.a", 
          "name": [
            "Laboratory Translational Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Jongen", 
        "givenName": "Jennifer M. J.", 
        "id": "sg:person.07511721061.48", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07511721061.48"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University Medical Center Utrecht", 
          "id": "https://www.grid.ac/institutes/grid.7692.a", 
          "name": [
            "Laboratory Translational Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Raats", 
        "givenName": "Danielle A.", 
        "id": "sg:person.01331432136.62", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331432136.62"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University Medical Center Utrecht", 
          "id": "https://www.grid.ac/institutes/grid.7692.a", 
          "name": [
            "Laboratory Translational Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rinkes", 
        "givenName": "Inne H. M. Borel", 
        "id": "sg:person.013100574355.78", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013100574355.78"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University Medical Center Utrecht", 
          "id": "https://www.grid.ac/institutes/grid.7692.a", 
          "name": [
            "Laboratory Translational Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kranenburg", 
        "givenName": "Onno", 
        "id": "sg:person.0736252500.60", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736252500.60"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/nrc2397", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000709422", 
          "https://doi.org/10.1038/nrc2397"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/acs.jmedchem.5b01760", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000960460"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ccr.2006.08.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009233232"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cellsig.2011.01.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010224748"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jid.2016.06.625", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010510221"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep26521", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010790201", 
          "https://doi.org/10.1038/srep26521"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.4479", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011343080"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/cas.12348", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015909917"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-14-1645", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017763317"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.tips.2012.01.005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018571465"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s004120050256", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019687555", 
          "https://doi.org/10.1007/s004120050256"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature13194", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020098338", 
          "https://doi.org/10.1038/nature13194"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1204326", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020232714", 
          "https://doi.org/10.1038/sj.onc.1204326"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1204326", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020232714", 
          "https://doi.org/10.1038/sj.onc.1204326"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/onc.2010.520", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022589162", 
          "https://doi.org/10.1038/onc.2010.520"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08268", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024778997", 
          "https://doi.org/10.1038/nature08268"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08268", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024778997", 
          "https://doi.org/10.1038/nature08268"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc704", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028740665", 
          "https://doi.org/10.1038/nrc704"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc704", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028740665", 
          "https://doi.org/10.1038/nrc704"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature15726", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029461127", 
          "https://doi.org/10.1038/nature15726"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bmcl.2016.02.026", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031932563"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.274.26.18201", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038063403"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2015.03.053", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040351532"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2015.03.053", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040351532"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.fob.2015.01.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041211619"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/cc.29756", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042018085"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m210656200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042583933"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0145219", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048013975"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature13181", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048862142", 
          "https://doi.org/10.1038/nature13181"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc2981", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052273406", 
          "https://doi.org/10.1038/nrc2981"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep40557", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053445000", 
          "https://doi.org/10.1038/srep40557"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm2007613", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055952452"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm2007613", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055952452"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-15-2380", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063215972"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3748/wjg.v21.i48.13447", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071373299"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3892/or.2013.2401", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071532377"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3892/or.2013.2401", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071532377"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1077672320", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082482123", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082710962", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083241024", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3390/cancers9050047", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085210320"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/acschembio.7b00370", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1090389317"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.21145", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091891233"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ajpath.2018.06.008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1105742270"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-12", 
    "datePublishedReg": "2019-12-01", 
    "description": "Reactive oxygen species (ROS) function as second messengers in signal transduction, but high ROS levels can also cause cell death. MTH1 dephosphorylates oxidized nucleotides, thereby preventing their incorporation into DNA and protecting tumour cells from oxidative DNA damage. Inhibitors of MTH1 (TH588 and (S)-crizotinib) were shown to reduce cancer cell viability. However, the MTH1-dependency of the anti-cancer effects of these drugs has recently been questioned. Here, we have assessed anti-tumour effects of TH588 and (S)-crizotinib in patient-derived 3D colorectal cancer cultures. Hypoxia and reoxygenation - conditions that increase intracellular ROS levels - increased sensitivity to (S)-crizotinib, but not to TH588. (S)-crizotinib reduced tyrosine phosphorylation of c-MET and ErbB3 whereas TH588 induced a mitotic cell cycle arrest, which was not affected by adding ROS-modulating compounds. Furthermore, we show that both compounds induced DNA damage that could not be prevented by adding the ROS inhibitor N-acetyl-L-cysteine. Moreover, adding ROS-modulating compounds did not alter the reduction in viability in response to TH588 and (S)-crizotinib. We conclude that TH588 and (S)-crizotinib have very clear and distinct anti-tumour effects in 3D colorectal cancer cultures, but that these effects most likely occur through distinct and ROS-independent mechanisms.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41598-018-37316-w", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1045337", 
        "issn": [
          "2045-2322"
        ], 
        "name": "Scientific Reports", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "9"
      }
    ], 
    "name": "Differential anti-tumour effects of MTH1 inhibitors in patient-derived 3D colorectal cancer cultures", 
    "pagination": "819", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "d2c8eeaf2278b946cff11b24f23e7aa1dd7e387c123578273f1c2d83844f0dc6"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30692572"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101563288"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41598-018-37316-w"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1111676556"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41598-018-37316-w", 
      "https://app.dimensions.ai/details/publication/pub.1111676556"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T08:58", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000326_0000000326/records_68451_00000000.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s41598-018-37316-w"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-37316-w'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-37316-w'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-37316-w'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-37316-w'


 

This table displays all metadata directly associated to this object as RDF triples.

228 TRIPLES      21 PREDICATES      68 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41598-018-37316-w schema:about anzsrc-for:11
2 anzsrc-for:1112
3 schema:author N3effbc5305984fed9190fad627b74879
4 schema:citation sg:pub.10.1007/s004120050256
5 sg:pub.10.1038/nature08268
6 sg:pub.10.1038/nature13181
7 sg:pub.10.1038/nature13194
8 sg:pub.10.1038/nature15726
9 sg:pub.10.1038/nrc2397
10 sg:pub.10.1038/nrc2981
11 sg:pub.10.1038/nrc704
12 sg:pub.10.1038/onc.2010.520
13 sg:pub.10.1038/sj.onc.1204326
14 sg:pub.10.1038/srep26521
15 sg:pub.10.1038/srep40557
16 https://app.dimensions.ai/details/publication/pub.1077672320
17 https://app.dimensions.ai/details/publication/pub.1082482123
18 https://app.dimensions.ai/details/publication/pub.1082710962
19 https://app.dimensions.ai/details/publication/pub.1083241024
20 https://doi.org/10.1016/j.ajpath.2018.06.008
21 https://doi.org/10.1016/j.bmcl.2016.02.026
22 https://doi.org/10.1016/j.ccr.2006.08.009
23 https://doi.org/10.1016/j.cell.2015.03.053
24 https://doi.org/10.1016/j.cellsig.2011.01.004
25 https://doi.org/10.1016/j.fob.2015.01.003
26 https://doi.org/10.1016/j.jid.2016.06.625
27 https://doi.org/10.1016/j.tips.2012.01.005
28 https://doi.org/10.1021/acs.jmedchem.5b01760
29 https://doi.org/10.1021/acschembio.7b00370
30 https://doi.org/10.1021/jm2007613
31 https://doi.org/10.1074/jbc.274.26.18201
32 https://doi.org/10.1074/jbc.m210656200
33 https://doi.org/10.1111/cas.12348
34 https://doi.org/10.1158/0008-5472.can-14-1645
35 https://doi.org/10.1158/0008-5472.can-15-2380
36 https://doi.org/10.1371/journal.pone.0145219
37 https://doi.org/10.18632/oncotarget.21145
38 https://doi.org/10.18632/oncotarget.4479
39 https://doi.org/10.3390/cancers9050047
40 https://doi.org/10.3748/wjg.v21.i48.13447
41 https://doi.org/10.3892/or.2013.2401
42 https://doi.org/10.4161/cc.29756
43 schema:datePublished 2019-12
44 schema:datePublishedReg 2019-12-01
45 schema:description Reactive oxygen species (ROS) function as second messengers in signal transduction, but high ROS levels can also cause cell death. MTH1 dephosphorylates oxidized nucleotides, thereby preventing their incorporation into DNA and protecting tumour cells from oxidative DNA damage. Inhibitors of MTH1 (TH588 and (S)-crizotinib) were shown to reduce cancer cell viability. However, the MTH1-dependency of the anti-cancer effects of these drugs has recently been questioned. Here, we have assessed anti-tumour effects of TH588 and (S)-crizotinib in patient-derived 3D colorectal cancer cultures. Hypoxia and reoxygenation - conditions that increase intracellular ROS levels - increased sensitivity to (S)-crizotinib, but not to TH588. (S)-crizotinib reduced tyrosine phosphorylation of c-MET and ErbB3 whereas TH588 induced a mitotic cell cycle arrest, which was not affected by adding ROS-modulating compounds. Furthermore, we show that both compounds induced DNA damage that could not be prevented by adding the ROS inhibitor N-acetyl-L-cysteine. Moreover, adding ROS-modulating compounds did not alter the reduction in viability in response to TH588 and (S)-crizotinib. We conclude that TH588 and (S)-crizotinib have very clear and distinct anti-tumour effects in 3D colorectal cancer cultures, but that these effects most likely occur through distinct and ROS-independent mechanisms.
46 schema:genre research_article
47 schema:inLanguage en
48 schema:isAccessibleForFree true
49 schema:isPartOf N50f5ee9e5651473892d67004ee444035
50 N6209f5f03be6435d8785637aecb6fc1d
51 sg:journal.1045337
52 schema:name Differential anti-tumour effects of MTH1 inhibitors in patient-derived 3D colorectal cancer cultures
53 schema:pagination 819
54 schema:productId N3ef0086a91ed4da2a8c03b8bc1c914ab
55 N4cbbb4a126544309b371e006ec48082d
56 N68666b09ba424986abeaa23cace65491
57 N76e2ae90714e495281b42eac7488307f
58 Ned625c8265494efe826731444d6e3a49
59 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111676556
60 https://doi.org/10.1038/s41598-018-37316-w
61 schema:sdDatePublished 2019-04-11T08:58
62 schema:sdLicense https://scigraph.springernature.com/explorer/license/
63 schema:sdPublisher Nd4bbea53256b450eaf880e4f4547b0a7
64 schema:url https://www.nature.com/articles/s41598-018-37316-w
65 sgo:license sg:explorer/license/
66 sgo:sdDataset articles
67 rdf:type schema:ScholarlyArticle
68 N2d872d6b319145f19e793a935228a5de rdf:first sg:person.01331432136.62
69 rdf:rest N9ffd660b61b54863a5cb8e04ec6f082d
70 N3ef0086a91ed4da2a8c03b8bc1c914ab schema:name pubmed_id
71 schema:value 30692572
72 rdf:type schema:PropertyValue
73 N3effbc5305984fed9190fad627b74879 rdf:first sg:person.012645335613.60
74 rdf:rest Ndffe70d1db274f9d8a65b76c2aa775b4
75 N4cbbb4a126544309b371e006ec48082d schema:name readcube_id
76 schema:value d2c8eeaf2278b946cff11b24f23e7aa1dd7e387c123578273f1c2d83844f0dc6
77 rdf:type schema:PropertyValue
78 N50f5ee9e5651473892d67004ee444035 schema:issueNumber 1
79 rdf:type schema:PublicationIssue
80 N6209f5f03be6435d8785637aecb6fc1d schema:volumeNumber 9
81 rdf:type schema:PublicationVolume
82 N68666b09ba424986abeaa23cace65491 schema:name dimensions_id
83 schema:value pub.1111676556
84 rdf:type schema:PropertyValue
85 N76e2ae90714e495281b42eac7488307f schema:name nlm_unique_id
86 schema:value 101563288
87 rdf:type schema:PropertyValue
88 N848fb08a002f4583814f0be07fb4e2a8 rdf:first sg:person.0736252500.60
89 rdf:rest rdf:nil
90 N9ffd660b61b54863a5cb8e04ec6f082d rdf:first sg:person.013100574355.78
91 rdf:rest N848fb08a002f4583814f0be07fb4e2a8
92 Nd4bbea53256b450eaf880e4f4547b0a7 schema:name Springer Nature - SN SciGraph project
93 rdf:type schema:Organization
94 Ndffe70d1db274f9d8a65b76c2aa775b4 rdf:first sg:person.01030512251.67
95 rdf:rest Nfe7e3c8fe6b84af981a6e12af27d5afe
96 Ned625c8265494efe826731444d6e3a49 schema:name doi
97 schema:value 10.1038/s41598-018-37316-w
98 rdf:type schema:PropertyValue
99 Nfe7e3c8fe6b84af981a6e12af27d5afe rdf:first sg:person.07511721061.48
100 rdf:rest N2d872d6b319145f19e793a935228a5de
101 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
102 schema:name Medical and Health Sciences
103 rdf:type schema:DefinedTerm
104 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
105 schema:name Oncology and Carcinogenesis
106 rdf:type schema:DefinedTerm
107 sg:journal.1045337 schema:issn 2045-2322
108 schema:name Scientific Reports
109 rdf:type schema:Periodical
110 sg:person.01030512251.67 schema:affiliation https://www.grid.ac/institutes/grid.7692.a
111 schema:familyName Laoukili
112 schema:givenName Jamila
113 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01030512251.67
114 rdf:type schema:Person
115 sg:person.012645335613.60 schema:affiliation https://www.grid.ac/institutes/grid.7692.a
116 schema:familyName van der Waals
117 schema:givenName Lizet M.
118 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012645335613.60
119 rdf:type schema:Person
120 sg:person.013100574355.78 schema:affiliation https://www.grid.ac/institutes/grid.7692.a
121 schema:familyName Rinkes
122 schema:givenName Inne H. M. Borel
123 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013100574355.78
124 rdf:type schema:Person
125 sg:person.01331432136.62 schema:affiliation https://www.grid.ac/institutes/grid.7692.a
126 schema:familyName Raats
127 schema:givenName Danielle A.
128 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331432136.62
129 rdf:type schema:Person
130 sg:person.0736252500.60 schema:affiliation https://www.grid.ac/institutes/grid.7692.a
131 schema:familyName Kranenburg
132 schema:givenName Onno
133 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736252500.60
134 rdf:type schema:Person
135 sg:person.07511721061.48 schema:affiliation https://www.grid.ac/institutes/grid.7692.a
136 schema:familyName Jongen
137 schema:givenName Jennifer M. J.
138 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07511721061.48
139 rdf:type schema:Person
140 sg:pub.10.1007/s004120050256 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019687555
141 https://doi.org/10.1007/s004120050256
142 rdf:type schema:CreativeWork
143 sg:pub.10.1038/nature08268 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024778997
144 https://doi.org/10.1038/nature08268
145 rdf:type schema:CreativeWork
146 sg:pub.10.1038/nature13181 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048862142
147 https://doi.org/10.1038/nature13181
148 rdf:type schema:CreativeWork
149 sg:pub.10.1038/nature13194 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020098338
150 https://doi.org/10.1038/nature13194
151 rdf:type schema:CreativeWork
152 sg:pub.10.1038/nature15726 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029461127
153 https://doi.org/10.1038/nature15726
154 rdf:type schema:CreativeWork
155 sg:pub.10.1038/nrc2397 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000709422
156 https://doi.org/10.1038/nrc2397
157 rdf:type schema:CreativeWork
158 sg:pub.10.1038/nrc2981 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052273406
159 https://doi.org/10.1038/nrc2981
160 rdf:type schema:CreativeWork
161 sg:pub.10.1038/nrc704 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028740665
162 https://doi.org/10.1038/nrc704
163 rdf:type schema:CreativeWork
164 sg:pub.10.1038/onc.2010.520 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022589162
165 https://doi.org/10.1038/onc.2010.520
166 rdf:type schema:CreativeWork
167 sg:pub.10.1038/sj.onc.1204326 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020232714
168 https://doi.org/10.1038/sj.onc.1204326
169 rdf:type schema:CreativeWork
170 sg:pub.10.1038/srep26521 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010790201
171 https://doi.org/10.1038/srep26521
172 rdf:type schema:CreativeWork
173 sg:pub.10.1038/srep40557 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053445000
174 https://doi.org/10.1038/srep40557
175 rdf:type schema:CreativeWork
176 https://app.dimensions.ai/details/publication/pub.1077672320 schema:CreativeWork
177 https://app.dimensions.ai/details/publication/pub.1082482123 schema:CreativeWork
178 https://app.dimensions.ai/details/publication/pub.1082710962 schema:CreativeWork
179 https://app.dimensions.ai/details/publication/pub.1083241024 schema:CreativeWork
180 https://doi.org/10.1016/j.ajpath.2018.06.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105742270
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1016/j.bmcl.2016.02.026 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031932563
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1016/j.ccr.2006.08.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009233232
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1016/j.cell.2015.03.053 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040351532
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1016/j.cellsig.2011.01.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010224748
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1016/j.fob.2015.01.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041211619
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1016/j.jid.2016.06.625 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010510221
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1016/j.tips.2012.01.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018571465
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1021/acs.jmedchem.5b01760 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000960460
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1021/acschembio.7b00370 schema:sameAs https://app.dimensions.ai/details/publication/pub.1090389317
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1021/jm2007613 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055952452
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1074/jbc.274.26.18201 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038063403
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1074/jbc.m210656200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042583933
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1111/cas.12348 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015909917
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1158/0008-5472.can-14-1645 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017763317
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1158/0008-5472.can-15-2380 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063215972
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1371/journal.pone.0145219 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048013975
213 rdf:type schema:CreativeWork
214 https://doi.org/10.18632/oncotarget.21145 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091891233
215 rdf:type schema:CreativeWork
216 https://doi.org/10.18632/oncotarget.4479 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011343080
217 rdf:type schema:CreativeWork
218 https://doi.org/10.3390/cancers9050047 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085210320
219 rdf:type schema:CreativeWork
220 https://doi.org/10.3748/wjg.v21.i48.13447 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071373299
221 rdf:type schema:CreativeWork
222 https://doi.org/10.3892/or.2013.2401 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071532377
223 rdf:type schema:CreativeWork
224 https://doi.org/10.4161/cc.29756 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042018085
225 rdf:type schema:CreativeWork
226 https://www.grid.ac/institutes/grid.7692.a schema:alternateName University Medical Center Utrecht
227 schema:name Laboratory Translational Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands
228 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...